Docstoc

UNIVERSITY OF NEBRASKA MEDICAL CENTER

Document Sample
UNIVERSITY OF NEBRASKA MEDICAL CENTER Powered By Docstoc
					PRMS Policies and Procedures




                    UNIVERSITY OF NEBRASKA MEDICAL CENTER

                               EPPLEY CANCER CENTER

              PROTOCOL REVIEW and MONITORING SYSTEM (PRMS)
                                  and
                 DATA and SAFETY MONITORING COMMITTEE

                          POLICIES AND PROCEDURES MANUAL




                                   UNMC Eppley Cancer Center
                                 986805 Nebraska Medical Center
                                     Omaha, NE 68198-6805
                               Eppley Science Hall 10006 and 10007
                                      Phone: (402) 559-4969
                                      Fax:    (402) 559-4970




PRMS Version 6.2
July 7, 2010




Version 6.2
June 14, 2010
PRMS Policies and Procedures



                                   CONTACT INFORMATION


                       ASSOCIATE DIRECTOR for CLINICAL RESEARCH
                                    Julie M. Vose, M.D.


                                    PRMS AUDIT COMMITTEE
                                    Elizabeth Reed, M.D., Chair


                    DATA and SAFETY MONITORING COMMITTEE (DSMC)
                              James R. Anderson, Ph.D., Chair


                               SCIENTIFIC REVIEW COMMITTEE (SRC)
                                    Terence Lawson, Ph.D., Chair

                                          PRMS STAFF
              Julie A. Maloney
    PRMS/Clinical Trials Program Manager                            Mirna Colón
       Eppley Science Institute 2001                         Regulatory Data Associate
            (402) 559-4232 office                           Eppley Science Institute 2002
             (402) 559-4970 fax                                 (402) 559-4969 office
                                                                 (402) 559-4970 fax

                                      PRMS/CTO WEBSITE

                                     http://www.unmc.edu/ccto
PRMS Policies and Procedures



OVERVIEW OF THE PRMS AND DSMC
   INTRODUCTION                                                                                                                                      1
   RELATIONSHIP BETWEEN THE SRC AND THE IRB                                                                                                          1
   RELATIONSHIP BETWEEN THE SRC, DSMC, and AUDIT COMMITTEES                                                                                          2
   TOXICITY AND ADVERSE EVENTS REPORTING (DSMC)                                                                                                      2
   ADHERENCE REPORTING (AUDIT COMMITTEE)                                                                                                             2
SCIENTIFIC REVIEW COMMITTEE (SRC)
   ADMINISTRATIVE POLICIES AND PROCEDURES                                                                                                              3
      Purpose                                                                                                                                          3
      Protocols That Require SRC Review                                                                                                                3
      Protocols That Do Not Require SRC Review                                                                                                         3
      Final Determination of Need for SRC Review............................................................................ 3
      Meeting Schedule ........................................................................................................................ 4
      Membership ................................................................................................................................. 4
        Appointment Terms .................................................................................................................... 4
        Voting and Non-Vosting Members.............................................................................................. 4
        Roles and Responsibilities ......................................................................................................... 5
   PROTOCOL SUBMISSIONS                                                                                                                                5
      Submission Deadlines ................................................................................................................ 5
      Types of Submissions................................................................................................................. 6
        New Protocols ............................................................................................................................ 6
        Continuing Review ..................................................................................................................... 6
        Change(s) in Protocol................................................................................................................. 6
        Expediated Review (Formerly Called SRC Exempt)................................................................... 6
      Submission Requirements ......................................................................................................... 7
        New Protocols ............................................................................................................................ 8
        Continuing Review ..................................................................................................................... .. 9
        Request for Change ................................................................................................................... .. 9
   PROTOCOL CLASSIFICATION SYSTEMS AND DEFINITIONS                                                                                                     9
      Sponsor Classifications .............................................................................................................. 9
        Investigator-Initiated Institutioanl Protocols ................................................................................ 10
        Mulit-Center Institional Protocols ................................................................................................ 10
        National Cooperative Group Trials ............................................................................................. 10
        Industrial Trials ........................................................................................................................... 10
        Other Externally Peer ReCooperative Group Trials                                                                                              10
      National Cencer Institute (NCI) Classifications ......................................................................... 10
        Therapeutic Intervetnion Trials ................................................................................................... 10
        Prevention Intervetnion Trials                                                                                                                10
        Non-Intervention Trials                                                                                                                       10
      Study Phase Classification (for therapeutic or prevention intervention protocols only) ...... 10
        Pilot Studies ............................................................................................................................... 11
        Phase I Intervention Studies                                                                                                                  11
        Phase II Intervention Studies                                                                                                                 11

             Phase III Intervention Studies..................................................................................................... 11
             Combination Phase Intervetnion Studies                                                                                              11
           Study Type Classification (for non-itervention protocols only) .............................................. 12
PRMS Policies and Procedures


         Screeening, Early Detection, or Diagnostic Trial ....................................................................... 12
         Supportive Care Trial ................................................................................................................. 12
         Epidemiologic/Observational Trial                                                                                                            12
         Ancillary or Companion Trial ...................................................................................................... 12
         Correlative Trial .......................................................................................................................... 12
   PRIORITIZATION                                                                                                                                     12
   OTHER REQUIREMTNES                                                                                                                                 13
   PROTOCOL REVIEW PROCEDURES                                                                                                                         13
       SRC Protocl Review Procedusres ............................................................................................. 13
         Assignment of Reviewers ........................................................................................................... 13
         Types of Reviews ....................................................................................................................... 13
         Reviewer Responsibilities........................................................................................................... 14
         Changes to the Protocol ............................................................................................................. 15
         Continuing Reviews.................................................................................................................... 15
         Continuing Review with Request for Change ............................................................................. 15
       Review Outcomes........................................................................................................................ 16
         New Protocol and Continuing Reviews ...................................................................................... 16
         Request for Change in Protocol Reviews ................................................................................... 16
       Voting Procedures ....................................................................................................................... 16
   REPORTING REQUIREMENTS                                                                                                                             17
       Accrual Reporting ....................................................................................................................... 17
       Study Completion ........................................................................................................................ 17
       Protocol Termination Or Withdrawal By The PI ........................................................................ 17
       Protocol Termination By The SRC ............................................................................................. 17
       Toxicity And Adverse Events Reporting To The DSMC ........................................................... 18
       Adherence Reporting To The Audit Committee ........................................................................ 18
PRMS AUDIT COMMITTEE
   Purpose                                                                                                                                            20
   Protocols Audited                                                                                                                                  20
   Protocols Not Audited                                                                                                                              20
   Audit Frequency                                                                                                                                    20
   Notification of Audit Findings                                                                                                                     20
   Duration of Audits                                                                                                                                 21
   Committee Membership and Length of Terms                                                                                                           21
       Members 2008 - 2009                                                                                                                            21
   Meetings                                                                                                                                           21
   Audit Procedures                                                                                                                                   21
       The Clinical Trials Program Manager‟s Role                                                                                                     21
       The Auditor‟s role                                                                                                                             21
   Protocol-Specific Audit Report Form                                                                                                                22
   Audit Documentation                                                                                                                                22
   Intranet and Open Forum Communications                                                                                                             22
APPENDIX A: DATA AND SAFETY MONITORING COMMITTEE (DSMC)
   ADMINISTRATIVE POLICIES AND PROCEDURES .......................................................................... 25
       Purpose                                                                                                                                        25
       Scope                                                                                                                                          25
       Reporting Relationships                                                                                                                        25
       Membership                                                                                                                                     25
PRMS Policies and Procedures


        Voting Members ......................................................................................................................... 25
        Appointment Terms .................................................................................................................... 25
        Administrative Support .............................................................................................................. 25
        Current Members ...................................................................................................................... 25
      Meeting Schedule                                                                                                                           25
      Roles and Responsibilities ......................................................................................................... 26
      Policies and Procedures ............................................................................................................ 26
   PROTOCOL SUBMISSION ................................................................................................................ 27
      Protocols That Require DSMC Review                                                                                                         27
      New Protocol Submissions                                                                                                                   28
      Changes to the Protocol's AE Reporting Guidelines                                                                                          28
      Review Procedure                                                                                                                           28
      Frequency of Monitoring                                                                                                                    29
   PROTOCOL MONITORING ................................................................................................................ 29
      Scheduled Review                                                                                                                           29
      Scheduled Adverse Event review Forms                                                                                                       29
      Phase III Investigator Initiated Therapeutic Studies                                                                                       30
   SERIOUS ADVERSE EVENT REVIEW .............................................................................................. 30
      Definition of a Serious Adverse Event                                                                                                      30
      Reporting Serious Advers Events                                                                                                            31
   REVIEW OF INTERIM ANALYES ...................................................................................................... 32
   SUBMISSION DEADLINES ................................................................................................................ 32
   PROTOCOL TERMINATION and CONCLUSION of DSMC REVIEW ............................................... 32
   REVIEW PROCEDURES ..................................................................................................................... 32
      Assignment of Review                                                                                                                       32
      Conflict of Interest Policy                                                                                                                33
      Review Outcomes                                                                                                                            33
        Review of New Protocol and/or Chages .................................................................................... 33
        Review of AE's and SAE's ......................................................................................................... 33
        Voting Procedures                                                                                                                        33
APPENDIC A.1: DSMC Report for Phase I Protocols ............................................................................ 34
APPENDIC A.2: DSMC Report for Pilot, Phase II and Phase II Studies ............................................... 35
APPENDIC A.3: Adverse Event Reporting Worksheet.......................................................................... 36
APPENDIX B: SRC SUBMISSION REQUIREMTNS ................................................................................. 37
APPENDIX C: UECC SRC PROTOCOL FORMAT ................................................................................... 38
APPENDIX D.1: New Protocol Submission Form................................................................................... 45
APPENDIX D.2: New Protocol Submission Form - Open at Children's ONLY ..................................... 45
APPENDIX E.1: Continuing Review Submission Form ......................................................................... 54
APPENDIX E.2: Continuing Review Submission Form - National Cooperative Group (NCG) ............ 57
APPENDIX E.3: Continuing Review Submission Form - NCG Open at Children's ONLY ................... 60
APPENDIX F.1: Request For Change Submission Form ....................................................................... 63
APPENDIX F.2: Request For Change Submission Form - Open at Children's ONLY ......................... 66
PRMS Policies and Procedures                                                                  Page 1 of 58


                               OVERVIEW OF THE PRMS AND DSMC
I. INTRODUCTION
    The Protocol Review and Monitoring System (PRMS) of the University of Nebraska Medical Center
    (UNMC) Eppley Cancer Center (Cancer Center) provides central management and oversight functions
    for all cancer related trials involving human subjects conducted by members of the Cancer Center.
    The PRMS Scientific Review Committee (SRC) is responsible for: 1) evaluating all new and amended
    clinical research protocols for scientific merit and to ensure that there are adequate resources available
    to successfully complete the proposed research; 2) monitoring accrual to active protocols to ensure
    that studies meet their accrual goals and to require a reassessment of recruitment strategies and/or
    accrual goals when necessary; 3) ensuring that there are no competing studies with overlapping
    eligibility criteria for a specific disease indication; and 4) establishing each protocol‟s priority based on
    NCI guidelines and institutional priorities. The SRC is also responsible for the ongoing annual scientific
    review of cancer center protocols.
    The PRMS Audit Committee audits all Cancer Center investigator-initiated, multi-center and other
    externally peer reviewed therapeutic intervention trials to ensure: 1) compliance with institutional
    regulatory guidelines; 2) confirmation of patient eligibility; 3) adherence to treatments; 4)
    appropriateness of adverse event monitoring and reporting; and 5) adequacy of patient follow-up as
    stipulated in the protocol.
    The DSMC monitors all internal toxicities and adverse events that occur on therapeutic intervention
    trials not monitored by an independent board specifically designed for the individual study to ensure
    that: 1) all investigator-initiated and multi-center institutional therapeutic intervention protocols include a
    definition of adverse events specific to the protocol; and 2) therapeutic intervention (i.e. disease
    related) protocols adhere to institutional, FDA, and CTEP guidelines for toxicity and adverse event
    reporting (CTE Common Toxicity Criteria can be obtained through the UNMC Eppley Cancer Center
    PRMS office or at http://ctep.info.nih.gov/CT3/ctc.htm).


II. RELATIONSHIP BETWEEN THE SRC AND THE IRB
    The SRC focuses on the scientific merit, prioritization, and progress of cancer-related research
    involving human subjects conducted by Cancer Center members and UNMC faculty members. The
    function of the SRC is complementary to that of the Institutional Review Board (IRB), and does not
    duplicate the responsibilities of the IRB, which focuses on the protection of human subjects.
    SRC approval is required before final release or continuation by the IRB is given. This requirement
    does not apply to protocols in follow-up where subject accrual is complete. The IRB will not issue full
    approval for any cancer-related study involving human subjects without first receiving notice of
    approval from the SRC, stating that all scientific requirements for the study have been met. On a case
    by case basis, however, the IRB may choose to review protocols before they have been submitted to
    the SRC.
    If the investigator fails to obtain SRC approval prior to expiration of the IRB approval period, the
    protocol will be classified as approval expired until all requirements are met.
    If a protocol is tabled by the SRC at the time of the continuing review, the IRB will review the IRB
    application for continuing review, but will restrict the protocol by halting enrollment of new subjects until

Version 6.2
June 14, 2010
PRMS Policies and Procedures                                                                 Page 2 of 74


    the required revisions are completed and SRC approval is granted. Currently enrolled subjects may be
    able to continue on the study, as determined by a case by case review.

III. RELATIONSHIP BETWEEN THE SRC, DSMC, and AUDIT COMMITTEES
    The SRC, DSMC, and Audit Committees function independently of one another. However, both the
    DSMC and Audit Committees submit monthly reports to the SRC for informational purposes. Each of
    these committees report to the Associate Director for Clinical Research of the Cancer Center. See
    Appendix A, page 23 of Error! Bookmark not defined.Error! Bookmark not defined. for a more
    complete description of the DSMC and page 19 of Error! Bookmark not defined.Error! Bookmark
    not defined. for a more complete description of the Audit Committee.

IV. TOXICITY AND ADVERSE EVENTS REPORTING (DSMC)
    All investigator-initiated and multi-center institutional therapeutic intervention protocols must include a
    definition of adverse events specific to the protocol. Therapeutic intervention (i.e. disease related)
    protocols must adhere to institutional, FDA, and CTEP guidelines for toxicity and adverse event
    reporting (CTE Common Toxicity Criteria can be obtained through the UNMC Eppley Cancer Center
    PRMS office or at http://ctep.info.nih.gov/CT3/ctc.htm).
    The UNMC Data and Safety Monitoring Committee (DSMC) monitors all internal toxicities and adverse
    events that occur on therapeutic intervention trials not monitored by an independent board specifically
    designed for the individual study.
    With the exception of transplant protocols, all internal serious adverse events (expected or unexpected,
    regardless of attribution) must be reported to the DSMC. For transplant protocols, The DSMC
    recognizes that certain toxicities are routinely anticipated. The investigator can indicate that a
    particular toxicity is anticipated for the vast majority of research participants and that such toxicity will
    therefore not be reported. The DSMC will determine in its initial review of the protocol if such exclusion
    from standard reporting guidelines is acceptable.

V. ADHERENCE REPORTING (AUDIT COMMITTEE)
    The Audit Committee audits and provides oversight of all Cancer Center investigator-initiated
    institutional, multi-center institutional and other externally peer reviewed therapeutic intervention trials
    not monitored by an outside body to insure compliance with institutional regulatory guidelines,
    confirmation of patient eligibility, adherence to treatments, appropriateness of adverse event monitoring
    and reporting, and adequacy of patient follow-up as stipulated in the protocol.
    If significant concerns are documented that are thought to compromise the safety or scientific integrity
    of the protocol (i.e. failure to comply with the approved study guidelines regarding adverse event
    reporting, eligibility criteria, stopping rules, quality data collection, etc.) the Audit Committee can
    request that the SRC evaluate the audit and determine if the protocol should be suspended until the
    issues are adequately addressed by the PI, the study must be closed, or the study can continue.
    All investigator-initiated institutional, multi-center institutional and other externally peer reviewed
    therapeutic intervention protocols will continue to be audited while patients are receiving protocol-
    specific treatment. Protocols will no longer be audited when subject accrual, treatment, and/or
    research related tests are completed.
    The Audit Committee provides a monthly report to the SRC of its review. See page 19 of 74 for a more
    complete description of the Audit Committee.
PRMS Policies and Procedures                                                             Page 3 of 74


                               SCIENTIFIC REVIEW COMMITTEE (SRC)

I. ADMINISTRATIVE POLICIES AND PROCEDURES
    A.   PURPOSE
         A functioning Scientific Review Committee (SRC) is a mandatory element of a National Cancer
         Institute (NCI) designated clinical cancer center. The SRC oversees the scientific aspects of
         cancer-related research involving human subjects conducted by members of the University of
         Nebraska Medical Center (UNMC) faculty and students, and members of the UNMC Eppley
         Cancer Center (UECC). The SRC facilitates the development of innovative, collaborative, and
         scientifically sound studies that focus on the prevention, detection, diagnosis, and treatment of
         cancer and its long-term follow-up and care. The SRC helps investigators to prioritize studies to
         ensure optimal allocation of UECC resources.
    B.   PROTOCOLS THAT REQUIRE SRC REVIEW
         All cancer-related protocols involving human subjects require SRC review.     Examples of cancer-
         related protocols that require SRC review include the following:
             Studies that require consent of human subjects and/or involve cancer patients
             Studies that have as a principal investigator a UNMC faculty member or a UECC member
             Therapeutic studies
             Late effects studies
             Quality of life studies
             Laboratory studies involving previously banked tissues
             Studies that investigate cancer etiology, prevention, or control
             Studies that investigate secondary cancer prevention such as early diagnosis and screening,
              symptom management during and following treatment, and survivorship
             Studies that investigate cancer risk factors such as dietary studies that involve surrogate
              endpoints (i.e. precancerous lesions such as polyps for colon cancer, genetic markers, and
              interventions for cancer prevention)
             Studies that require consent of human subjects that address the specific effects of a cancer
              diagnosis or its related treatments on family members and/or healthy controls if they are
              matched or dyadic with cancer patients
             Studies of medical devices for cancer management
    C.   PROTOCOLS THAT DO NOT REQUIRE SRC REVIEW
          Database infrastructure protocols
          Cancer Control, Quality of Life (QOL), and prevention, screening, and detection studies
            involving healthy subjects that do not have cancer as a disease end-point or outcome
          Studies that involve the promotion of a healthy lifestyle in healthy subjects without a cancer
            endpoint
          Studies that require a one time emergency IRB approval to treat a specific cancer patient
    D.   FINAL DETERMINATION OF NEED FOR SRC REVIEW
         When a Principal Investigator (PI) believes a protocol is exempt from SRC Review, the PI may
         request that a preliminary review be conducted by the SRC Chair. Once a preliminary
         determination is made, it must be confirmed by the entire SRC at the next regularly scheduled
         meeting. The IRB review continues to be required.
PRMS Policies and Procedures                                                               Page 4 of 74


         Questions regarding whether a particular protocol requires SRC review can be directed to the
         UECC Clinical Trails Program Manager at (402) 559-4232, UNMC Campus Zip 6805.

         Final determination of whether or not a protocol requires SRC review will be made by the SRC.

    E.   MEETING SCHEDULE
         SRC meetings are held on the second Monday of each month. A list of scheduled meetings and
         SRC submission deadlines is available from the UECC PRMS office, 559-4969, UNMC Campus
         Zip 6805 or on the PRMS/CTO website at http://www.unmc.edu/ccto/.

          Note: The SRC meets one time each month and has no process for expedited review should
          the submission deadline for the regularly scheduled meeting be missed
         .
         Investigators may request that a Subcommittee of the SRC review new protocols or changes to a
         previously approved protocol (see SRC Section VI.A.2, page 13 of Error! Bookmark not
         defined.Error! Bookmark not defined.. To be eligible for a subcommittee review, one of the
         following conditions must apply:
         1. The sponsor or funding agency‟s deadline is such that consideration at a regularly scheduled
            SRC meeting would not be feasible given the time constraints and the study represents an
            important research venture for the PI and UNMC or involves an important therapeutic option
            for patients.
         2. The proposed protocol change(s) involves an important therapeutic option for a potential
            patient already identified by the investigator and directly affects that patient‟s ability to begin
            treatment as outlined in the protocol.
         Although the subcommittee may grant approval to the investigator, the decision must be
         confirmed by the entire SRC at the following meeting. The IRB review remains required.
    F.   MEMBERSHIP
         1. Appointment Terms: Members are appointed for three year terms that can be renewed at
            the discretion of the SRC Chair. All SRC members receive an orientation to the SRC and a
            copy of the SRC manual.
         2. Voting and Non-voting Members: SRC members are appointed by the UNMC Eppley
            Cancer Center Director. Voting members include one biostatistician, one community
            member, and representatives of academic units/departments. Non-voting members include
            an IRB representative and the PRMS/Clinical Trials Program Manager. At large or additional
            ad hoc members with specific expertise not already present on the SRC may be appointed.
            Academic units include, but are not limited to the following:

                 Adult Oncology/Hematology                          Obstetrics and Gynecology
                 College of Dentistry                               Pathology/Microbiology
                 College of Nursing                                 Pediatric Oncology/Hematology
                 College of Pharmacy                                Radiation Oncology
                 Eppley Research Institute                          Surgery
                 Head and Neck Surgery/Otolaryngology
PRMS Policies and Procedures                                                                   Page 5 of 74


         3. Roles and Responsibilities:
              Chair
               Appointed by the UECC Director
               Chairs monthly SRC meetings
               Performs protocol reviews
               Corresponds with investigators
               Orients new members to SRC policies and procedures
               Reports to the Associate Director for Clinical Research, Director of the UECC and the
                 Chancellor of UNMC
              Vice-Chair
               A voting member of the SRC appointed by the Chair
               Assumes the chair‟s duties as needed
               Reports to the Chair of the SRC
              PRMS/CTO Program Manager
               Assigns reviews to committee members
               Records meeting minutes
               Generates correspondence to investigators following the SRC‟s review
               Maintains data on protocols reviewed by the SRC
               Generates protocol and accrual reports
               Generates the NCI Summary 4 report
               Assists investigators in preparing submissions
               Ensures adherence of protocol submission formats and supporting documentation
               Maintains data on patient accrual
               Maintains the data in the UECC database
               Participates in new study coordinator training
               Obtains annual feedback on the SRC Policies and Procedures from SRC members, PIs
                 and study coordinators
               Consults on the design and revisions of the PRMS/CTO website
               Ensures that a copy of the current SRC manual is available at all SRC meetings
               Reports to the Associate Director for Clinical Research, Assistant Director for Research
                 Administration and to the Director of the UECC
         4. Current Members: A list of current members is available in the PRMS Office.

II. PROTOCOL SUBMISSIONS
    A. SUBMISSION DEADLINES
        The SRC submission deadline is the 4th Friday of every month, unless otherwise noted on the list
        of scheduled meetings and SRC submission deadlines. A list of scheduled meetings and SRC
        submission deadlines is available from the UECC PRMS office or on the PRMS/CTO Website at
        http://www.unmc.edu/ccto/.
        Submissions to the SRC should be made directly to the PRMS Office (ECI, Rooms 2001) or via
        campus mail (UNMC zip 6805).
PRMS Policies and Procedures                                                                       Page 6 of 74


        Please Note: Protocols received in the PRMS office after the submission deadline will only be
        scheduled for review at the next scheduled SRC meeting if one of the following two conditions
        apply:
         1. The sponsor or funding agency‟s deadline is such that consideration at a subsequent SRC
            meeting would not be feasible given the time constraints and the study represents an
            important research venture for the PI and UNMC.
         2. The proposed protocol change(s) involves an important therapeutic option for a potential
            patient already identified by the investigator and directly affects that patient‟s ability to begin
            treatment as outlined in the protocol.
        Late submissions that do not meet one of the above conditions will be held for review at a
        subsequent SRC meeting.
    B. TYPES OF SUBMISSIONS
        1.    New Protocol: Any new protocol that is cancer-related involving human subjects.
                    New protocol submission requirements are defined in SRC Section II.C.1, page 8 of 74.
                    See SRC Section I.B, page 3 of 74 for what constitutes a cancer-related protocol.
                    See Appendix B, page 37 of 74 for a bulleted list of SRC new protocol submission
                     requirements by SRC classification.
                    See Appendix C, page 38 of 74 for directions on creating a protocol in UECC SRC
                     Protocol Format
                   Note: Protocols in UECC SRC format are required for the following types of
                   submissions:
                    Investigator-Initiated Institutional Therapeutic Intervention studies
                    Investigator Initiated Institutional Prevention Intervention studies
                    Investigator Initiated Institutional Ancillary/Companion studies
                    Therapeutic Intervention Pilot studies
        2.    Continuing Review: All protocols must be reviewed 11 months from the original IRB
              approval date and no later than 12 months from the date of the last review thereafter.
              Protocols may require more frequent continuing review by either the SRC or the IRB.
                     See Appendix E, page 50 of 74 and Appendix F, page 58 of 74, for required forms and
                      format.

        3.    Change(s) in Protocol: Any change to Institutional, Industrial or Other Externally Peer
              Review protocols (i.e., change in personnel, study design, drug dosing, etc.) must be
              reviewed and approved by the SRC. This applies to protocols that are actively accruing
              subjects as well as those in follow-up. See Appendix G, page 64 of 74, for required forms and
              format.
              Changes to National Cooperative Group trials do not require SRC review or approval.
              However, changes that are made to the protocol since the last Continuing Review must be
              listed when submitting the next Continuing Review.
        4.     Expedited Review (Formerly Called SRC Exempt)
              All cancer-related protocols require initial review by the SRC to determine whether or not
              ongoing SRC review is necessary. Many specimen studies, medical record reviews, and
PRMS Policies and Procedures                                                                               Page 7 of 74


              projects involving existing documents or records may be considered for Expedited Review.
              Some examples of such research include:
                    Anonymous surveys
                    Retrospective chart reviews
                    Analysis of discarded pathological specimens without personal identifiers
                    Protocols involving previously consented patients
                    Proposals involving previously banked materials and/or tissues
                    Protocols to obtain tissue or other biological samples for prospective or undetermined
                     future research
              While the full SRC is ultimately responsible for deciding whether a study requires ongoing
              SRC review, investigators may ask the SRC Chair or his/her designee to conduct an
              Expedited Review, which will be presented to the full SRC at it‟s next regularly scheduled
              meeting for confirmation.
              Investigators who believe that their research qualifies for SRC Expedited Review must submit
              a copy of the completed IRB application to the SRC for review. Because the SRC reviews the
              science of a project and the IRB reviews projects to ensure the protection of human subjects,
              the SRC and IRB forms ask for different information. It is the PI‟s responsibility to ensure that
              the IRB application contains sufficient information for the SRC Chair to make an initial
              determination as to whether a protocol requires ongoing SRC review.
              If the SRC Chair is unable to make an initial determination of ongoing review status from the
              IRB application alone, the PI will be asked to submit a completed SRC “New Project” form.
              Occasionally, the PI may be asked to complete a full SRC “New Project” submission, if the
              initial determination is that the protocol may require ongoing SRC review. The full SRC
              submission will be processed in the same manner as all other New Project submissions

                 Note: Once it has been determined that a protocol does not require ongoing SRC review, the
                 protocol will not be subject to further SRC review unless a major change is made to the protocol that
                 would affect the science of the study. Examples of major changes that may make the study eligible
                 for ongoing SRC review are:
                    Changes in the study‟s design, methods and/or procedures
                    Changes in the study‟s drug dose or delivery
                    Changes in the eligibility criteria for the study
                    Whenever an investigator develops specific plans for cancer-related research involving the
                     samples obtained by the study

              It is the Investigator‟s responsibility to notify the SRC when major changes are made to a
              protocol. This should be done by submitting a completed SRC “Request for Change” form.
              All of the current SRC forms, the instructions for completing the forms, and the SRC
              submission deadline/meeting calendar may be found on the PRMS/CTO website at
              http://www.unmc.edu/ccto/.

    C. SUBMISSION REQUIREMENTS

          Note: Investigators should note that submitting an incomplete new protocol, continuing
          review or change form or a submission utilizing outdated forms may result in a delayed
          SRC review or may cause the protocol to be tabled.

          For New Protocol SRC Review Forms, see Appendix D page 39 of 52.
PRMS Policies and Procedures                                                                              Page 8 of 74




        1.    New Protocols: The most current New Protocol submission form is available from the
              UECC PRMS office or on the PRMS/CTO Website at http://www.unmc.edu/ccto/. The form is
              also included as Appendix D on page 45 of Error! Bookmark not defined.Error! Bookmark
              not defined. of this document.
              All new protocol submissions must include the following supplementary documents:
                 Original Signed and Dated SRC New Protocol Submission Form
                 Cover letter and/or copy of relevant correspondence (if applicable)
                 Copy of the IRB Application for Biomedical Research form – Sections I and II
                 Consent form/s (if applicable)
                 Data collection form/s (required for all Investigator-Initiated Institutional trials)
                 Investigator Brochure (if applicable)
                 Grant application (if applicable)
                 Protocol with version and date clearly marked on the face page
              a. Investigator-Initiated Institutional Protocols: Must be submitted in the UECC SRC
                 format (see Appendix C, page 38 of Error! Bookmark not defined.Error! Bookmark not
                 defined.). Assistance in preparing a protocol in cancer center format may be obtained by
                 contacting the UNMC Eppley Cancer Center PRMS office.
              b. Multi-Center Institutional, National Cooperative Group, Industrial and Other
                 Externally Peer Reviewed Protocols: May be submitted without conversion to UNMC
                 Eppley Cancer Center format, provided they contain the key elements required by the
                 SRC scientific review, along with a completed SRC Review Form.
              c. Therapeutic or Prevention Intervention Pilot Protocols: Intervention pilot protocols
                 should follow the SRC protocol format. The following items should be addressed in the
                 protocol: 1) justification of sample size; 2) estimated duration of study; 3) methods of
                 analyses; 4) decision-making criteria; and 5) criteria for stopping the trial earlier than
                 planned . A new protocol submission form is required (see Appendix D, page 45 of
                 Error! Bookmark not defined.Error! Bookmark not defined.).
              d. Non-Intervention Pilot Protocols: For non-intervention pilot protocols, the IRB
                 application and a brief discussion of the specifics of the research plan is sufficient for
                 submission.
                  If the research involves laboratory-based procedures, these should be outlined in
                  sufficient detail to allow for scientific review by the SRC. A statistical section should be
                  included that addresses the following: 1) the estimated duration of study; 2) the method of
                  analyses; 3) the decision-making criteria; and 4) the criteria for stopping the trial earlier
                  than planned. Clear criteria for knowing whether or not the aims have been met should
                  be part of the application, even if statistics per se are not applicable.
                  For instrument development studies, the statistical section should include: 1) applicable
                  validity/accuracy and reliability/precision to be assessed; 2) what method will be used for
                  each; 3) the proposed sample size and its rationale based on both the validity and
                  reliability estimates to be made and the coefficient to be used; 4) the analysis proposed
                  for each validity and reliability estimate; 5) the coefficient to be used; and 6) the target
                  criterion.
PRMS Policies and Procedures                                                                       Page 9 of 74


              e. Non-Intervention Protocols: With the exception of Investigator Initiated protocols, non-
                 intervention protocols do not need to be in SRC protocol format. In most cases, the IRB
                 application and a brief discussion of the specifics of the research plan and the
                 biostatistical considerations, when appropriate, will be sufficient. If the research involves
                 laboratory-based procedures, they should be outlined in sufficient detail to allow for
                 scientific review by the SRC. Non-intervention protocols include the following types: 1)
                 Screening, Early Detection or Diagnostic trials; 2) Supportive Care trials; 3)
                 Epidemiologic/Observational trials; 4) Ancillary or Companion trials; and 4) Correlative
                 trials
        2.    CONTINUING REVIEW: There are two Continuing Review submission forms; one for
              National Cooperative Group trials and one for Institutional, Industrial and Other Peer
              Reviewed trials. The most current Continuing Review submission forms are available from the
              PRMS office or on the PRMS/CTO Website at http://www.unmc.edu/ccto/. The forms are also
              included as Appendix E, page 50 of Error! Bookmark not defined.Error! Bookmark not
              defined. (for Institutional, Industrial and Other Peer Reviewed trials) and Appendix F, page 58
              of Error! Bookmark not defined.Error! Bookmark not defined. (for National Cooperative
              Group trials) of this document.
              All continuing reviews must include the following supplementary documents:
               Original Signed and Dated SRC Continuing Review Submission Form
               Cover letter and/or copy of relevant correspondence (if applicable)
               Copy of the IRB Application for Continuing Review form - Section I and II
               Copy of the consent form(s)
               The REVISED protocol, with version and date clearly marked on the face page (if
                   applicable)

        3.    REQUEST FOR CHANGE: The most current Request for Change submission form is
              available from the PRMS office or on the PRMS/CTO website at http://www.unmc.edu/ccto/.
              The form is also included as Appendix G, page 64 of Error! Bookmark not defined.Error!
              Bookmark not defined. of this document.
              All requests for change must include the following supplementary documents:
               Original Signed and Dated SRC Request for Change Submission Form
               Cover letter and/or copies of any correspondence related to this change (if applicable)
               Copy of the IRB Request for Change and/or Consent form – Section I and II (if applicable)
               The REVISED consent form(s) (if applicable)
               The REVISED Data collection form(s) (if applicable)
               The REVISED Investigator Brochure (if applicable)
               Copy of the schema and abstract from the grant (If the proposed change, including title
                   change, is the result of a new request for financial support)
               The REVISED protocol with version and date clearly marked on the face page

III. PROTOCOL CLASSIFICATION SYSTEMS AND DEFINITIONS
    All cancer-related protocols must be categorized using the following classification system. While the
    SRC is ultimately responsible for determining a protocols classification, the PI is asked to utilize the
    following definitions to provide a preliminary classification of their protocols on the new protocol
    submission forms (See Appendix D, page 45 of Error! Bookmark not defined.Error! Bookmark not
    defined.).
PRMS Policies and Procedures                                                                      Page 10 of 74


    1. Sponsor Classification:
        A.    Investigator-Initiated Institutional Protocols: Trials that are designed and developed by a
              local investigator that may or may not receive external support, and may include collaborative
              studies conducted with industry in which the local Principal Investigator (PI) is the primary
              contributor to the design, implementation, and monitoring of the trial. These trials may be a:
               Single-site trial: involving only UNMC/Nebraska Medical Center
               Multi-site trial: the local PI implementing protocol at more than one clinical site
               Industry-sponsored trial: the study is receiving some funding from industry
        B.    Multi-Center Institutional Protocols: Trials that involve a local PI participating in cancer-
              related studies originating at another institution. These protocols are designed by informal
              cooperative groups or consortia in order to generate sufficient accrual to answer a scientific
              question. Such protocols are typically reviewed at the participating institutions, but do not
              receive Cancer Therapy Evaluation Program (CTEP) review. More than one IRB approval is
              required for multi-center protocols.
        C.    National Cooperative Group Trials: Trials that are initiated by NCI funded study groups and
              receive CTEP review. NOTE: Only those study groups listed below qualify for this
              classification.
                 ACRIN - American College of Radiology Imaging Network
                 ASSOG - American College of Surgeons Oncology Group
                 CALGB - Cancer and Leukemia Group B
                 COG - Children‟s Oncology Group
                 ECOG - Eastern Cooperative Oncology Group
                 EORTC - European Organization for Research and Treatment of Cancer
                 GOG - Gynecologic Oncology Group
                 NCI CA - National Cancer Institute of Canada, Clinical Trials Group
                 NSABP - National Surgical Adjuvant Breast and Bowel Project
                 NCCTG - North Central Cancer Treatment Group
                 RTOG - Radiation Therapy Oncology Group
                 SWOG - Southwest Oncology Group
        D.    Industrial Trials: Trials that are designed and monitored by industry. The local PI has had
              little or no input as to the form or content of the protocol. The design and implementation of
              the study is controlled by the sponsor. The level of industry support may vary and may
              include any of the following: agent/drug supplies, use of an external laboratory, or funding.
        E.    Other Externally Peer-Reviewed Trials: R01, P01 or other trial funded by NIH or supported
              by other peer-reviewed funding organizations, such as the ACS, the Komen Foundation, etc.
    2. National Cancer Institute (NCI) Classification
        A.    Therapeutic Intervention Trials: Trials that are designed to test new cancer treatments (i.e.
              new drugs, new approaches to surgery or radiation therapy, new combinations of treatments,
              or new methods, such as gene therapy).
        B.    Prevention Intervention Trials: Trials of drugs to prevent cancer in subjects who have never
              had cancer or to prevent the recurrence of cancer.
        C.    Non-Intervention Trials: Trials that do not include an intervention.
    3. Study Phase Classification (for therapeutic or prevention intervention protocols only)
PRMS Policies and Procedures                                                                      Page 11 of 74


        A.    Pilot Studies: These are studies in which the primary objective is to collect preliminary data
              to plan a future protocol. Included in this category are studies preparatory to the development
              of an application for independent peer-reviewed support, or to take maximum advantage of a
              unique research opportunity or idea in the basic, clinical, and/or population sciences. These
              protocols may attempt to demonstrate the feasibility of conducting a randomized trial in a
              particular patient population. Included in this category are pilot trials that attempt to test an
              application or intervention in both an experimental and a control group, as well as feasibility
              studies that test an application or intervention in an experimental group only. These trials
              must be limited in duration (i.e., 1-2 years depending upon the nature of the research) and the
              investigator must specify future plans.
        B.    Phase I Intervention Studies: Studies that determine a safe dose or therapy for Phase II
              trials and define acute effects that occur with a relatively high frequency in normal tissues. In
              addition, these trials may examine the drug‟s pharmacology and may reveal evidence of anti-
              tumor activity. Therapeutic intent is always present in Phase I trials; anticancer drugs are
              usually not tested in patients unless preclinical activity studies have demonstrated evidence of
              significant activity in lab models. The initial starting dose in humans must be justified in the
              protocol. The initial dose may be increased gradually by some defined procedure until a level
              is found which produces limiting, but tolerable toxicity and/or clear signs of therapeutic
              activity.
        C.    Phase II Intervention Studies: Studies that determine whether a drug or therapy has anti-
              tumor activity in a defined patient population and estimates the response rate in a defined
              patient population. Well designed Phase II trials do not permit the entry of more patients than
              is necessary to ensure the presence or absence of a clinically significant level of activity.
              Because various tumor types have different prognostic factors, eligibility requirements and
              patterns of responsiveness to a particular drug or combination of drugs or therapy, Phase II
              trials are conducted in homogenous clinical entities (i.e., metastatic breast cancer patients
              with measurable disease and a normal or near normal performance status).
        D.    Phase III Intervention Studies: If significant activity is observed in any disease during Phase
              II testing, subsequent clinical trials usually compare the new drug or treatment modality with
              standard treatment or observation, if no standard treatment exists. Relevant endpoints (i.e.,
              time to progression, survival, quality of life) must be used to measure benefit.
        E.    Combination Phase Intervention Studies: Studies that are a combination of phases such
              as Phase I/II or II/III.
PRMS Policies and Procedures                                                                           Page 12 of 74


    4. Study Type Classification (for non-intervention protocols only)
        A.    Screening, Early Detection, or Diagnostic Trial: Protocol designed to test the efficacy of
              devices, techniques, procedures, or tests for earlier/more accurate detection or diagnosis of
              disease.
        B.    Supportive Care Trial: Protocol designed to improve the comfort and quality of life for the
              patient.
        C.    Epidemiologic/Observational Trial: Study among cancer patients and healthy populations
              that involve no intervention or alteration in the status of the participants (e.g., surveillance, risk
              assessment, environmental and behavioral studies, etc.)
        D.    Ancillary or Companion Trial: Auxiliary study that is stimulated by, but not a required part
              of, a main clinical trail, and that utilizes patient or other resources of the main trial to generate
              information relevant to it.

              NOTE: Companion or ancillary studies must be linked to an active trial, or epidemiologic or
              other observational study (screening, early detection, diagnostic; therapeutic; or prevention
              trial) and should include only patients accrued to that trial or study.


        E.    Correlative Trial: Laboratory based study using specimens to assess cancer risk, clinical
              outcomes, response to therapies, etc.

              NOTE: Correlative studies must be linkable to other patient data.


IV. PRIORITIZATION
    Newly proposed research should not compete with other protocols with similar objectives or eligibility
    criteria. Occasionally, the SRC will approve a competing protocol if it meets one of the following
    criteria: 1) when it is necessary to have a portfolio rather than a single Phase I study available to allow
    for interruption in accrual for safety analysis after accrual of limited cohorts; 2) when a study is
    targeted to the same disease and stage but has only a slight overlap in eligibility criteria such as age,
    tumor biology or prior treatment history; 3) when the competing study is expected to be completed in
    the very near future; or 4) when the competing studies are active at different clinical sites.
    If competing protocols exist, the PI must adequately address the issue of prioritization and rank. While
    the final priority designation is the responsibility of the SRC, PIs are asked to utilize the current Priority
    Listing for Intervention and for Non-Intervention trials posted on the PRMS/CTO website
    (http://eppleyprms.com/) to make a preliminary priority designation. Protocols are ranked as follows:
    1st Priority - Investigator-initiated Institutional trials
    2nd Priority - Multi-Center Institutional trials
    3rd Priority - National Cooperative Group trials
    4th Priority - Industrial trials
    5th Priority - Other Externally Peer Reviewed trials
PRMS Policies and Procedures                                                                     Page 13 of 74


V. OTHER REQUIREMENTS
    In addition to the requirements outlined in Sections I through IV above, PIs are responsible for real-time
    reporting of the following to the PRMS: 1) accrual of all participants; 2) when a study is closed to
    accrual, completed or terminated; and 3) toxicity, adverse events, and adherence reports.

VI. PROTOCOL REVIEW PROCEDURES
    A. SRC PROTOCOL REVIEW PROCEDURES
        1. Assignment of Reviewers: The SRC Administrator considers conflict of interest when
           assigning and distributing protocols and reviewer sheets to primary, secondary, and
           biostatistical reviewers. When the expertise is not present in the SRC membership to give a
           peer-review of a protocol, ad-hoc reviewers are asked to review the protocol. If a SRC member
           serves as a primary or secondary investigator, a consultant (including a biostatistician), or
           study coordinator on a protocol submitted for SRC review, that individual will not be allowed to
           serve as a reviewer for that protocol. While this SRC member may be present for the
           discussion of the protocol, he or she will abstain from voting.
              New Investigator-initiated, Multi-Center and Industrial Submissions require a primary,
               secondary, and statistical review. All therapeutic intervention protocols will be reviewed by
               at least one clinician.
              New Cooperative Group Submissions require one primary reviewer and are reviewed for
               prioritization only.
              Continuing Review and Request for Change Submissions require one primary reviewer
               and, at the discretion of the SRC Chair, a biostatistical review.

                Note: Changes to National Cooperative Group trials do not require SRC review or
                approval. However, changes that are made to the protocol since the last Continuing
                Review should be listed when submitting the next Continuing Review form.


        2. Types of Reviews
              Full Board Review: All protocols require full board review except those requesting minor
               changes
              Subcommittee Review: Requests for a SRC subcommittee to review new protocols must
               be made directly to the PRMS Office. To be eligible for a subcommittee review, one of the
               following two conditions must apply:
                a.    The sponsor or funding agency‟s deadline must be such that consideration at a
                      scheduled SRC meeting would not be feasible given the time constraints.
                b.    The study represents an important research venture for the PI and UNMC or involves
                      an important therapeutic option for patients.
                The PRMS/CTO Program Manager will contact the SRC Chair, who may decide that the
                submission can be sent for SRC subcommittee review and will designate three SRC
                members to perform an expedited review. The review team will include at least one
                biostatistician, and the review will be concluded within five working days. Although the
PRMS Policies and Procedures                                                                     Page 14 of 74


                subcommittee may grant approval to the investigator, the decision must be confirmed by the
                entire SRC at the following meeting. The IRB review remains required.
              Administrative Review: The PRMS/CTO Program Manager forwards all requests for minor
               changes in protocol submissions to the SRC Chair to determine whether administrative
               review or full board review is required. In addition, continuing reviews of National
               Cooperative Group trails are administratively reviewed by the SRC Chair.
                Although the Chair may grant approval to the investigator, the decision must be confirmed
                by the entire SRC at the following meeting. The IRB review remains required.
        3. Reviewer Responsibilities:
              Conflict of Interest: If an SRC member serves as a primary or secondary investigator, a
               consultant (including a biostatistician), or study coordinator on a protocol that is submitted
               for SRC review, that individual will not be allowed to serve as a reviewer for that protocol.
               While the SRC member may be present for the discussion of the protocol, he or she will
               abstain from voting.
              Primary, Secondary, and Biostatistical Reviewers for Investigator-initiated
               Institutional, Multi-Center Institutional, and Industrial protocols: Reviewers are
               responsible for written reviews and comments on the following:
                a. Objectives: Are the objectives and endpoints of the protocol clearly defined?
                b. Scientific Rationale: Does the protocol address relevant scientific questions?
                c. Study Design: Does the proposed protocol design address the protocol‟s objectives
                   and scientific rationale? Can the proposed objectives be met with available resources
                   of the UECC? Can the objectives be met within an acceptable time frame? Does the
                   study design include appropriate stopping criteria?
                d. Methodology: Are the methods in the protocol adequate to answer the questions
                   addressed in the objectives? Are there resources available within the UECC to conduct
                   these methods? For therapeutic intervention protocols, is there a description of the
                   agent‟s activity, dose delivery and scheduling, and dose modification criteria?
                e. Statistics: Is the statistical design clearly described, well-defined, and statistically
                   sound? Are the accrual goals clearly stated? Is the sample size adequate to answer
                   the specific objectives of the protocol? For qualitative studies, are appropriate
                   analytical design and decision criteria included?
                f.   Data Collection: Will the data collected answer the objectives of the protocol? Are the
                     data collection and analysis methods clearly described and sound? Data forms are
                     considered an essential part of the protocol and must be submitted to the SRC with the
                     initial submission. The SRC may withhold review and approval of a protocol pending
                     submission and review of data collection forms.
                g. Prioritization: Is the priority relative to other competing protocols clearly stated?
                   According to NCI guidelines, institutional protocols must be given highest priority
                   followed by national cooperative group trials, industrial protocols, and lastly, other
                   externally peer reviewed trails.
               Primary, Reviewers for National Cooperative Group Trials: Reviewers are responsible
                for written reviews and comments on prioritization only.
PRMS Policies and Procedures                                                                     Page 15 of 74


               Primary Reviewer for Change(s) in Protocol: Reviewers are responsible for written
                review and comments regarding all changes in protocol. It should be noted that whenever a
                change is necessary to better protect research subjects, (for example, one that is the result
                of a toxicity or adverse event report) the IRB is obligated to approve or disapprove that
                change immediately and IRB continuation will not therefore, be contingent upon SRC
                approval. However, the investigator should understand that continuance of the study is
                dependent upon SRC approval of the changes. The reviewer will provide a summary of the
                proposed change and make recommendations to the SRC. Depending on the nature of the
                change, the SRC may request that a biostatistician review the proposed revisions to the
                protocol.
        4. Changes to the Protocol:
               Minor Changes: Minor changes to the protocol will be reviewed and approved
                administratively. Examples of minor changes include a change in study title, study
                personnel, and the addition or deletion of a study site that does not change the overall
                accrual.
               Major Changes: Major changes to the protocol are sent to the SRC for full board review.
                Examples of major changes include modifications in drug dosage or delivery; change in
                methods, procedures or study design; changes in exclusion or inclusion criteria; and
                addition/reduction of subject accrual goals.
               Subcommittee Review of a Major Change: An investigator may petition the SRC for a
                subcommittee review of a major change in protocol. The PI must contact the PRMS Office
                and demonstrate that delaying implementation of the protocol change until the next
                scheduled meeting of the SRC would seriously impede the research project. The
                PRMS/CTO Program Manager will contact the SRC chair, who may decide that the
                submission can be sent for SRC subcommittee review and will designate three SRC
                members to perform an expedited review. Although the subcommittee may grant approval
                to the investigator, the decision must be confirmed and approved by the entire SRC at the
                following meeting.
               Changes to National Cooperative Group Trials: Changes to National Cooperative Group
                trials do not require SRC review or approval. However, changes that are made to the
                protocol since the last Continuing Review must be listed when submitting the next
                Continuing Review.
        5. Continuing Reviews: The purpose of a continuing review is to: 1) determine if sufficient
           progress is being made; 2) monitor protocol compliance; 3) review adverse events meeting
           DSMC reporting criteria; 4) monitor patient accrual; and 5) monitor changes in the study
           priority. Some protocols may require continuing review more frequently than the 11 month
           cycle. Continuing reviews will be conducted on all protocols that are active with ongoing
           accrual. A final review is conducted if a study is active, but accrual is complete.
        6. Continuing Review with Request for Change: Changes to the protocol submitted with the
           continuing review will be reviewed by the entire SRC unless the SRC is notified in advance of a
           need for an administrative or subcommittee review of the changes.
PRMS Policies and Procedures                                                                     Page 16 of 74


    B. REVIEW OUTCOMES
        1. New Protocol and Continuing Reviews: After the reviewer(s) complete their review of the
           New Protocol and/or Continuing submission, the reviewer(s) recommend that the SRC take
           one of the following actions:
               Full Approval: The study is scientifically sound and acceptable as written. Full approval is
                given and the IRB and PI are notified.
               Conditional Approval: The study is scientifically sound and acceptable if clarifications are
                provided. Full approval will be withheld until the necessary clarifications are made and
                approved by the SRC Chair.
               Approval with Revisions: The study is scientifically sound and acceptable if the PI makes
                modifications to the protocol. Full approval is withheld until the protocol is revised to
                incorporate the recommended modifications. The protocol must be re-reviewed and
                approved by the original SRC reviewers.
               Tabled: The study must be re-submitted in its entirety to the SRC for full-board review with
                significant modifications and responses to the questions raised by the SRC during its initial
                review.
               Disapproved: The study is not scientifically sound or ethical.
        2. Request for Change in Protocol Reviews: After the reviewer(s) complete their review of the
           Request for Change in Protocol, the reviewer(s) recommend that the SRC take one of the
           following actions:
               Full Approval: Change(s) to the study are scientifically sound and acceptable as written.
               Conditional Approval: Change(s) to the study are scientifically sound and acceptable if
                clarifications are provided. Full approval of the change(s) will be held until the necessary
                modifications are made and approved by the SRC Chair.
               Approval with Revisions: Change(s) to the study are scientifically sound and acceptable
                if the PI makes modifications. Full approval of the change(s) will be held until the protocol
                is revised to incorporate the recommended modifications and protocol is approved by the
                original SRC reviewers.
               Disapproved: Change(s) to the study are not scientifically sound or ethical, not acceptable
                as written, or not within the mission of the UNMC Eppley Cancer Center and cannot be
                implemented.
    C. VOTING PROCEDURES: The review motion must be seconded and be approved by a majority
       vote of those present.
PRMS Policies and Procedures                                                                     Page 17 of 74


VII. REPORTING REQUIREMENTS
     A. ACCRUAL REPORTING
         One function of the SRC is to monitor accrual on all cancer-related protocols. Each PI is
         responsible for submitting copies of signed consents to the PRMS office within one week
         of consent. If accrual information is not forwarded on a timely basis, the SRC may elect to
         suspend the trial to further accrual.
         If a signed consent form does not contain a UNMC Medical Record number, the following
         demographic information must also be included with each consent form:
             Patient‟s date of birth
             Patient‟s gender
             Patient‟s ethnicity
         Once a study is closed to accrual, the SRC should be notified in writing. If the SRC is notified
         between continuing review cycles that a study has closed to accrual, one final SRC continuing
         review is required. If a protocol change is required at a later date, the change must be submitted
         to the SRC for review.

     B. STUDY COMPLETION
        When a study is closed, (i.e. all follow-up is completed and all data have been analyzed), the PI
        should promptly inform the SRC in writing.

     C. PROTOCOL TERMINATION or WITHDRAWAL BY THE PI
        The SRC should be promptly notified of protocols terminated or withdrawn from SRC/IRB
        consideration by the PI.

     D. PROTOCOL TERMINATION BY THE SRC
        If a trial is terminated or suspended by the SRC, the PI will be notified along with the reason(s) for
        the actions. The investigator will have 30 days to appeal in writing. The investigator‟s appeal will
        be reviewed at the following meeting of the SRC. If the investigator cannot adequately address the
        concerns of the SRC, the appeal will be denied. The IRB will be notified in writing of the outcome
        of the appeal.
        If the SRC‟s review results in the need to modify the IRB application and/or consent(s), the
        appropriate revisions should be submitted to both the SRC and IRB. If no response to the SRC‟s
        review is received within 60 calendar days, the protocol will be classified as withdrawn and must be
        resubmitted to the SRC for full board review if the PI wishes reconsideration. A recommendation
        for protocol termination or suspension may occur at the time of continuing review for the following
        reasons:
        1. Insufficient accrual within the projected time period, defined as less than 30% of the projected
           accrual by the time of the second continuing review
        2. Failure to comply with early stopping criteria or planned interim analysis
        3. Serious adverse events beyond what would be expected for the procedure
PRMS Policies and Procedures                                                                         Page 18 of 74


     E. TOXICITY AND ADVERSE EVENTS REPORTING TO THE DSMC
         All investigator-initiated and multi-center institutional therapeutic intervention protocols must
         include a definition of adverse events specific to the protocol. Therapeutic intervention (i.e.
         disease related) protocols shall adhere to institutional, FDA, and CTEP guidelines for toxicity and
         adverse event reporting (CTE Common Toxicity Criteria can be obtained through the UNMC
         Eppley Cancer Center PRMS office or at http://ctep.info.nih.gov/CT3/ctc.htm).
         The UNMC Data and Safety Monitoring Committee (DSMC) monitors all internal toxicities and
         adverse events that occur on therapeutic intervention trials not monitored by an independent
         board specifically designed for the individual study and provides a monthly report to the SRC of its
         review. See Appendix A, page 23 of Error! Bookmark not defined.Error! Bookmark not
         defined.for a more complete description of the DSMC.
        With the exception of transplant protocols, all internal serious adverse events (expected or
        unexpected, regardless of attribution) must be reported to the DSMC. For transplant protocols, the
        DSMC recognizes that certain toxicities are routinely anticipated. The investigator can indicate that
        a particular toxicity is anticipated for the vast majority of research participants and that such toxicity
        will therefore not be reported. The DSMC will determine in its initial review of the protocol if such
        exclusion from standard reporting guidelines is acceptable.


     F. ADHERENCE REPORTING TO THE AUDIT COMMITTEE
        The Audit Committee audits and provides oversight of all Cancer Center investigator-initiated
        institutional, multi-center institutional and other externally peer reviewed therapeutic intervention
        trials not monitored by an outside body to insure compliance with institutional regulatory guidelines,
        confirmation of patient eligibility, adherence to treatments, appropriateness of adverse event
        monitoring and reporting, and adequacy of patient follow-up as stipulated in the protocol.
        If significant concerns are documented that are thought to compromise the safety or scientific
        integrity of the protocol (i.e. failure to comply with the approved study guidelines regarding adverse
        event reporting, eligibility criteria, stopping rules, quality data collection, etc.) the Audit Committee
        can request that the SRC evaluate the audit and determine if 1) the protocol should be suspended
        until the issues are adequately addressed by the PI, 2) the study must be closed, or 3) the study
        can continue.
        All investigator-initiated institutional, multi-center institutional and other externally peer reviewed
        therapeutic intervention protocols will continue to be audited while patients are receiving protocol-
        specific treatment. Protocols will no longer be audited when subject accrual, treatment, and/or
        research related tests are completed.
        The Audit Committee provides a monthly report to the SRC of its review. See the Audit Section,
        page 19 of Error! Bookmark not defined.Error! Bookmark not defined. for a more complete
        description of the Audit Committee.
PRMS Policies and Procedures   Page 19 of 74
PRMS Policies and Procedures                                                                       Page 20 of 74


                                      PRMS AUDIT COMMITTEE
I.   Purpose
     The Audit Committee performs audits and provides oversight on all UNMC Cancer Center
     Investigator-Initiated, Multi-Center and Other Externally Peer Reviewed clinical trials. The Audit
     Committee assures compliance with institutional regulatory guidelines, confirmation of subject
     eligibility, adherence to treatments, appropriateness of adverse event monitoring and reporting, and
     adequacy of subject follow-up as stipulated in the protocol.

II. Protocols Audited
     All therapeutic intervention cancer protocols that are Investigator-Initiated, Multi-Center or Other
     Externally Peer Reviewed and are not monitored by an external review body are audited by the
     committee.

III. Protocols Not Audited
     All therapeutic intervention cancer protocols that are Investigator-Initiated, Multi-Center or Other
     Externally Peer Reviewed and that are monitored by an external review body, such as the Industrial
     sponsor or it‟s designee, or by an NCI-funded cooperative group are not audited by the committee.


IV. Audit Frequency
     While any cancer-related protocol involving human subjects may be at risk for audit at any time by the
     audit committee, Investigator-Initiated, Multi-Center or Other Externally Peer Reviewed protocols are
     audited at least annually. The frequency of audit is dependent upon the phase of the protocol. Audits
     are scheduled based on the protocol‟s type of phase.

     A. Pilot, Phase I, Phase II and BMT trials – audited at least 4 times per year
     B. Phase III trials – audited at least 3 times per year

V. Notification of Audit Findings:
     Audit Committee Members: Audit results, using the protocol-specific audit report forms, are
     distributed to all members of the Audit Committee in advance of their scheduled meetings. The
     committee meets monthly to review the audit report(s) and to review the protocol if needed.
     Principal Investigator (PI): The Audit Committee notifies the PI in writing of the audit findings. The
     Audit Committee may request further information and/or follow-up from the PI. Typically a PI‟s written
     response to this request is expected within 30 days, although a more timely response may be required
     in some circumstances.
     Scientific Review Committee (SRC): Audit findings are reported to the SRC on a monthly basis. If
     significant concerns are documented that are thought to compromise the safety or scientific integrity of
     the protocol (i.e. failure to comply with the approved study guidelines regarding adverse event
     reporting, eligibility criteria, stopping rules, quality data collection, etc.) the Associate Director for
     Clinical Research or a member of the Audit Committee can request that the SRC evaluate the audit
     and determine if 1) the protocol should be suspended until the issues are adequately addressed by
     the PI, 2) the study must be closed, or 3) if the study can continue.
PRMS Policies and Procedures                                                                      Page 21 of 74


VII. Duration of Audits:
     All Investigator-Initiated, Multi-Center or Other Externally Peer Reviewed therapeutic intervention
     protocols will continue to be audited while subjects are receiving protocol-specific treatment.
     Protocols will no longer need to be audited when subject accrual, treatment, and/or research related
     tests are completed.

VIII. Committee Membership and Length of Terms:
     The Associate Director of Clinical Research appoints the Chair and members to the committee for a
     three year term, which can be renewed. The Audit Committee consists of at least three UNMC
     Cancer Center members.

     A. Members 2009 - 2010:
        Elizabeth Reed, M.D. –Chair and Associate Professor, Adult Oncology/Hematology
        M. Anne Kessinger, M.D. – Professor, Adult Oncology/Hematology
        Constance Visovsky, Ph.D. - Associate Professor, College of Nursing

X. Meetings:
     The Audit Committee routinely meets on a monthly basis to review audited protocols.

XI. Audit Procedures:
     A. The Clinical Trials Program Manager’s role:
        1. Orients new members to the Audit Committee
        2. Develops the annual audit schedule
        3. Sends the first notification of the impending audit at least 30 days prior to the scheduled audit
            date to the PI and the Study Coordinator, along with the current accrual list to be reviewed by
            the study coordinator/data manager for any updates or corrections and additional of off study
            dates.
        4. Makes necessary accrual updates and corrections in the CTO database.
        5. Selects at least one (1) randomly selected eligible subject record to audit, but no more than
            10% of the total accrual.
        6. Sends the second notification of the scheduled audit to the PI and the Study Coordinator
            identifying the specific subject(s) to be audited.
        7. Creates the agenda and minutes for the audit committee meetings.
        8. Emails the Audit Committee agenda and minutes, the SRC and DSMC report and the audit
            reports to the audit committee members for review.
        9. Attends the audit committee meeting
        10. Generates the audit finding letter, which is reviewed and signed by the Audit Chair and
            distributes the letter to the PI, Study Coordinator, the Associate Director of Clinical Research,
            and the IRB.
        11. Ensures that a copy of the Audit Committee Policies and Procedures is available at all Audit
            Committee meetings.

     B. The Auditor’s role:
        1. Generates a protocol-specific audit report form to use in performing the audit, conducts the
           audit and completes the audit report.
PRMS Policies and Procedures                                                                      Page 22 of 74


         2. Discusses the audit findings and any deviations in protocol with the Clinical Trails Program
            Manger prior to the monthly meeting.
         3. Answers any questions the committee may have regarding the audit report as needed.

XII. Protocol-Specific Audit Report Form:
     The protocol-specific audit report is derived from the following information contained within the
     protocol:
     A. Compliance with informed consent and eligibility requirements
     B. Treatment administration according to protocol guidelines
     C. Toxicity and adverse event reporting to the IRB and to the DSMC
     D. Appropriate follow-up

XIII. Audit Documentation:
     All audit documentation is maintained in the UNMC Eppley Cancer Center Clinical Trials Office, Room
     2002 of the Eppley Institute.

XIV. Intranet and Open Forum Communications:
     Current Policies and Procedures of the PRMS Audit Committee are available thru the UNMC Eppley
     Cancer Center Clinical Trails Office or on their web site at http://www.unmc.edu/ccto/.
     Periodic open forums are scheduled with study coordinators and PIs to communicate and clarify audit
     procedures and obtain feedback to streamline and facilitate the audit process.
DSMC Policies and Procedures                                           Page 23 of 74




     APPENDIX A: DATA AND SAFETY MONITORING COMMITTEE (DSMC)

                               UNIVERSITY OF NEBRASKA MEDICAL CENTER

                                       EPPLEY CANCER CENTER

                         DATA AND SAFETY MONITORING COMMITTEE (DSMC)

                                     POLICIES AND PROCEDURES




First Edition, Version 1.0, January 2006
Revised: Version 2.0, October 9, 2009
           Version 2.1, July 9, 2010
DSMC Policies and Procedures                                                     Page 24 of 74




                               CONTACT INFORMATION


                       ASSOCIATE DIRECTOR for CLINICAL RESEARCH
                                    Julie M. Vose, M.D.



               DATA and SAFETY MONITORING COMMITTEE (DSMC) CHAIR
                              James R. Anderson, Ph.D.


                                     DSMC MEMBERS
                                  R. Gregory Bociek, M.D.
                                Fausto R. Loberiza, Jr., M.D.
                                    Lori J. Maness, M.D.
                                  Elizabeth C. Reed, M.D.
                                    Lisa D. Runco, MPA
                                 Weining (Ken) Zhen, M.D.



                EPPLEY CANCER CENTER CLINICAL TRIALS OFFICE STAFF

          Julie A. Maloney, CCRP                                 Mirna Colón
    PRMS/Clinical Trials Program Manager                  Regulatory Data Associate
        Eppley Science Hall 10007                         Eppley Science Hall 10006
            (402) 559-4232 office                            (402) 559-4969 office
             (402) 559-4970 fax                               (402) 559-4970 fax
                                   PRMS/CTO WEBSITE

                                 http://www.unmc.edu/ccto
DSMC Policies and Procedures                                                               Page 25 of 74


I.   ADMINISTRATIVE POLICIES AND PROCEDURES
     A. PURPOSE
        The University of Nebraska Medical Center (UNMC) Data and Safety Monitoring Committee is
        assigned with the responsibility to monitor the safety of research participants in clinical trials
        conducted by UNMC Eppley Cancer Center (UECC) members, as outlined in the UNMC Eppley
        Cancer Center revised Institutional Data and Safety Monitoring Plan, Version 2.0 dated November
        19, 2004.

     B. SCOPE
        The UNMC Data and Safety Monitoring Committee (DSMC) reviews and monitors patient safety
        on all cancer related protocols involving human subjects that are classified as investigator initiated
        therapeutic intervention trials by the UECC Scientific Review Committee. Details on the
        submission and review process are described in section II.A and in Figure 1.

     C. REPORTING RELATIONSHIPS
        The UNMC Data and Safety Monitoring Committee reports to the UECC Associate Director for
        Clinical Research. Minutes from the DSMC meetings are submitted to the UNMC Scientific
        Review Committee (SRC), the UNMC Audit Committee and the UNMC Institutional Review Board
        (IRB), for informational purposes. Initial review of protocols is coordinated with the initial review by
        the Scientific Review Committee, to decrease the submission burden for investigators.

     D. MEMBERSHIP
        1. Voting Members: The DSMC consists of six voting members; four Cancer Center members
           actively involved in clinical research, a biostatistician, and a patient advocate.
         2.    Appointment Terms: Members and the Chair are appointed for five year terms by the
               UNMC Eppley Cancer Center Director. Terms can be renewed at the discretion of the UNMC
               Eppley Cancer Center Director.
         3.    Administrative Support: The DSMC is supported by a non-voting administrator assigned
               by the Clinical Trials Office of the Eppley Cancer Center.
         4.    Current Members: A list of current members is available in the ECC Clinical Trials Office.

     E. MEETING SCHEDULE
        The DSMC meets at least monthly on the Friday immediately preceding the second Monday of the
        month. Additional meetings for expedited full board review of Serious Adverse Events (SAE‟s) can
        be called at the discretion of the DSMC Chair. Meetings may be performed through email at the
        discretion of the DSMC Chair, if no items requiring full board review are on the agenda. .
DSMC Policies and Procedures                                                        Page 26 of 74
         A list of scheduled meetings and DSMC submission deadlines is available from the UECC CTO
         office, 559-4969, UNMC Campus Zip 6805 or on the PRMS/CTO website at
         http://www.unmc.edu/ccto/.

     F. ROLES AND RESPONSIBILITIES:
         Chair
          Appointed by the UECC Director
          Chairs monthly DSMC meetings
          Performs protocol reviews
          Corresponds with investigators
          Orients new members to DSMC policies and procedures
          Reports to the Associate Director for Clinical Research, Director of the UECC and the
            Chancellor of UNMC
         Acting Chair
          A voting member of the DSMC appointed by the Chair
          Assumes the Chair‟s duties as needed
          Reports to the Chair of the DSMC
         UECC CTO Program Manager
          Creates the annual list of scheduled AE reviews and distributes to applicable study personnel
          Assigns reviews to committee members
          Records meeting minutes
          Generates correspondence to investigators following the DSMC‟s review
          Ensures adherence of DSMC submission formats and supporting documentation
          Maintains data on protocols reviewed by the DSMC in the UECC database and in electronic
            and paper files
          Obtains annual feedback on the DSMC Policies and Procedures from DSMC members,
            Principal Investigators and study coordinators
          Ensures that a copy of the current DSMC Polices and Procedures and the DSMC Plan is
            available at all DSMC meetings
          Reports to the Associate Director for Clinical Research, Assistant Director for Research
            Administration and to the Director of the UECC

     G. POLICIES AND PROCEDURES
        The DSMC policies and procedures are reviewed every two (2) years by the DSMC Chair and the
        CTO program manager. Minor changes or adjustments (e.g. typographical errors, change in
        membership) can be made by the CTO program manager and approved by the DSMC chair. Any
        major changes or adjustments need to be reviewed and approved by the Associate Director for
        Clinical Research
DSMC Policies and Procedures                                                           Page 27 of 74


II. PROTOCOL SUBMISSION
     A. PROTOCOLS THAT REQUIRE DSMC REVIEW
        All cancer-related protocols involving human subjects that are classified as investigator initiated
        therapeutic intervention trials by the Eppley Cancer Center‟s Scientific Review Committee (SRC)
        require review by the UNMC Data and Safety Monitoring Committee (DSMC).
        To be classified as an investigator initiated intervention trial, the protocol must be designed and
        developed by a Principal Investigator (PI) who is an ECC member and be a clinical trial with a
        therapeutic intent using an agent or device (e.g. device, drugs, radiation, surgery, and/or
        biological agents).
DSMC Policies and Procedures                                                            Page 28 of 74

         Protocols designated as investigator-initiated therapeutic intervention trials with participation by
         multiple institutions must be monitored by an institutional DSMC or an independent data and
         safety monitoring board specifically designed for the individual study. Review by the Principal
         Investigator or a sponsor‟s Medical Monitor is not considered an independent review, and does
         not meet DSMC review requirements. It is the responsibility of the principal investigator to
         distribute the Data and Safety Monitoring Plan and the DSMC Policies and Procedures to all
         participating institutions and to ensure adherence to the Adverse Event reporting guidelines by all
         participating institutions.

         The algorithm in Figure 1 can be used to determine if a protocol requires review and monitoring by
         the UECC DSMC.

     B. NEW PROTOCOL SUBMISSIONS
        New cancer related protocols must be submitted for review to the SRC, as outlined in the SRC
        policies and procedures. Those protocols that require monitoring by the DSMC will be forwarded
        to the DSMC for initial review by the CTO.

         The DSMC will review the protocol, with a particular focus on the paragraphs pertaining to
         Adverse Event Reporting Guidelines and Toxicity (Section 9 in the UECC SRC protocol format).
         The DSMC will communicate its recommendations regarding changes to the protocol or protocol
         conduct to the PI in writing. The DSMC will also report its recommendations to the SRC Chair,
         and the SRC will incorporate these recommendations into the SRC review process.

         Submissions to the SRC and to the DSMC should be made directly to the UECC CTO (ECI,
         Rooms 5003) or via campus mail (UNMC zip 6805).

     C. CHANGES TO THE PROTOCOL’S AE REPORTING GUIDELINES
        Significant changes made to previously reviewed paragraphs pertaining to Adverse Event
        Reporting Guidelines and Toxicity (Section 9 in the UECC SRC protocol format) in protocols that
        are reviewed and monitored by the DSMC, require reviewe and approval as outlined in Section
        II.B above. If immediate changes are required to protect the safety of research subjects the
        DSMC chair can grant conditional approval of such changes pending review of the proposed
        changes by the full DSMC.

     D. REVIEW PROCEDURE
        During initial protocol review or review of significant changes to the paragraphs pertaining to
        Adverse Event Reporting Guidelines and Toxicity reviewers will pay special attention to whether
        the protocol contains:
         A clear and unambiguous definition of the instrument that will be used to grade Adverse
            Events (CTCAE vs. 3.0 recommended, but alternatives acceptable as long as they are clearly
            defined)

             A clear and unambiguous definition of Adverse Events
DSMC Policies and Procedures                                                                Page 29 of 74

             A clear and unambiguous description of all Adverse Events that will be reported to the DSMC.
              In general the DSMC expects all AE‟s grade 3 or higher (using CTCAE vs. 3.0), expected or
              unexpected and regardless of attribution, to be reported. The DSMC recognizes that certain
              toxicities are routinely anticipated on certain protocols (e.g. grade 4 hematologic toxicity on
              transplant protocols, etc.). The investigator can indicate that a particular toxicity is anticipated
              for the vast majority of research subjects and that such toxicity will therefore not be reported.
              The DSMC will determine in its initial review of the protocol if such exclusion from standard
              reporting guidelines is acceptable.
             A clear and unambiguous description of dose escalation and de-escalation criteria that will be
              used, including a clear definition of dose limiting toxicity, where relevant.
             Stopping rules for excessive toxicity and/or lack of efficacy where relevant
             A need for interim analysis

     E. FREQUENCY OF MONITORING
        In its initial review the DSMC will make a recommendation for the frequency of DSMC monitoring
        based on an assessment of risk associated with protocol therapy:
         Quarterly review, if the risk for protocol associated adverse events is considered significant
         Semi-annual review if the risk for protocol-associated adverse events is considered low
         Annual review is the risk for protocol associated adverse events is considered very low

         The frequency of monitoring can be changed based on the frequency or severity of adverse
         events encountered. A change in the frequency of monitoring will be communicated to the
         protocol principal investigator in writing.

III. PROTOCOL MONITORING

     A. SCHEDULED REVIEW
        Scheduled review of cumulative internal adverse events (AE‟s) by the DSMC takes place as
        outlined in the UNMC Eppley Cancer Center revised Institutional Data and Safety Monitoring Plan.
        The level of monitoring reflects the level of risk associated with the protocol. During the review the
        DSMC will pay particular attention to the frequency and severity of expected adverse events, the
        occurrence of unexpected adverse events, and the correct attribution of all reported adverse
        events.

     B. SCHEDULED ADVERSE EVENT REVIEW FORMS
        A protocol specific Data and Safety Monitoring Report (see appendices A.1 and A.2) must be
        submitted to the DSMC upon notification of a scheduled AE review. This report must be
        accompanied by a hard copy of the DSMC AE Reporting Worksheet (see appendix A.3) that
        summarizes all grade 3 or higher internal AE‟s (including SAE‟s that have been fully reported and
        reviewed by the DSMC). The AE Reporting Worksheet must also be submitted electronically in
        sortable format to the UECC CTO Manager. Electronic forms are available on the PRMS/CTO
        website at http://www.unmc.edu/ccto/.
DSMC Policies and Procedures                                                              Page 30 of 74

         Submissions to the DSMC should be made directly to the UECC CTO (ECI, Rooms 5003) or
         via campus mail (UNMC zip 6805). Electronic submissions should be made to the UECC CTO
         Manager via email at jamaloney@unmc.edu.
         A list of DSMC submission deadlines is available from the UECC CTO office, 559-4969, UNMC
         Campus Zip 6805 or on the PRMS/CTO website at http://www.unmc.edu/ccto/.

         Results of the DSMC review of the Data and Safety Monitoring Report and the AE Worksheet will
         be communicated in writing to the PI, to the Scientific Review Committee, to the Associate
         Director of Clinical Research and to the IRB.

     C. PHASE III INVESTIGATOR INITIATED THERAPEUTIC STUDIES:
        In accordance with NCI policy, each NIH-supported Phase III trial must have a protocol-specific
        data and safety monitoring board (DSMB). The principal investigator may elect to use the
        UNMC/Eppley Cancer Center DSMC as the DSMB for their Phase III study. These protocols will
        be reviewed with data provided for each arm of the study while maintaining the blinding of the
        study arms if applicable. Interim analyses for major protocol endpoints will be performed as
        outlined in the protocol. Blinding of the study arms, if applicable, will be maintained during the
        interim analyses. The DSMC may request unblinding of study arms or other protocol adjustments
        if the incidence or severity of adverse events differs significantly between protocol arms..

         If the PI does not choose to utilize the DSMC as the DSMB for their Phase III study, the
         composition and review procedures of the protocol-specific DSMB must be approved by the
         EUCC Associate Director for Clinical Research.

         NOTE REGARDING MULTI-SITE STUDIES: It is essential that all AE‟s for protocols initiated
         by a UNMC principal investigator at multiple institutions be monitored by the DSMC or a single
         board specifically designed for the individual study. For multi-site studies, all AE’s that occur
         at participating site’s must be reported as outlined for internal AE’s in Section III of this
         document (see pages thru Error! Bookmark not defined.6).
         It is the responsibility of the principal investigator to distribute the Data and Safety Monitoring
         Plan and the DSMC Policies and Procedures to all participating institutions and to ensure
         adherence to the Adverse Event reporting guidelines by all participating institutions.


IV. SERIOUS ADVERSE EVENT REVIEW
     Principal Investigators are responsible for reporting Internal Serious Adverse Events (SAE‟s) as
     outlined in the protocol and the UECC Institutional Data and Safety Monitoring Plan.

     A. DEFINITION OF A SERIOUS ADVERSE EVENT
        An Internal Adverse Event is serious and should be fully reported when the patient outcome is:
        1. Death: Any death that occurs while the subject is being treated on protocol or occurs within
             30 days of completing research related interventions.
DSMC Policies and Procedures                                                               Page 31 of 74


         2.    Life-Threatening: When the subject was at substantial risk of dying at the time of the
               adverse event or it is suspected that the use or continued use of the study drug or device
               would result in the subject‟s death.
         3.    Hospitalization (initial or prolonged): An admission to the hospital or prolongation of a
               hospital stay that is the result of an adverse event.
         4.    Disability: If the adverse event resulted in a significant, persistent, or permanent change,
               impairment, damage or disruptions in the patient's body function/structure, physical activities
               or quality of life.
         5.    Congenital Anomaly: If there are suspicions that exposure to a medical product prior to
               conception or during pregnancy resulted in an adverse outcome in the child.
         6.    Requires Intervention to Prevent Permanent Impairment or Damage: If it is suspected
               that the use of a medical product may result in a condition which required medical or surgical
               intervention to preclude permanent impairment or damage to a patient.

     B. REPORTING SERIOUS ADVERSE EVENTS
        Any Internal AE that meets one or more of the definitions of SAE outlined in Section IV.A above
        (see page 30) and/or meets the UNMC IRB‟s requirements for reporting must be fully reported to
        the DSMC. The principal investigator is responsible for submitting a copy of the IRB‟s Internal AE
        or Fatal AE (FE) Report Form along with a blinded copy of any related patient source documents
        to the DSMC.

         NOTE RE: MULTI-SITE STUDIES: For multi-site studies that are monitored by the DSMC, all
         SAE’s that occur at participating site’s must be reported as outlined for internal SAE’s in
         Section IV of this document (see pages 30 thru 31).
         It is the responsibility of the principal investigator to distribute the Data and Safety Monitoring Plan
         and the DSMC Policies and Procedures to all participating institutions and to ensure adherence to
         the Adverse Event reporting guidelines by all participating institutions.

         SAE‟s should be fully reported to the DSMC at the same time that they are reported to the IRB. In
         general, reporting of SAE‟s to the DSMC is expected within seven (7) business days of the
         occurrence of the event. If additional information about the SAE is still being collected a
         preliminary report should be filed within seven (7) business days with final reporting when
         additional information is available. Failure to report an SAE as required will be considered a
         protocol violation and may be reported to the Associate Director for Clinical Research.
DSMC Policies and Procedures                                                            Page 32 of 74


V. REVIEW OF INTERIM ANALYSES
     Protocols that are monitored by the DSMC may contain stopping rules for excessive toxicity or lack of
     efficacy. Whenever an interim analysis is performed to ensure that no protocol defined stopping rules
     have been met, a copy of the analysis must be forwarded to the DSMC. The DSMC will acknowledge
     the receipt of the analysis and discuss the results at its next regularly scheduled meeting.

VI. SUBMISSION DEADLINES
     The DSMC submission deadline is the 4th Friday of every month, unless otherwise noted on the list of
     scheduled meetings and DSMC submission deadlines.
     Submissions to the DSMC may be made directly to the UECC CTO (ECI, Rooms 5003) or via campus
     mail (UNMC zip 6805).

     A list of scheduled meetings and DSMC submission deadlines is available from the UECC CTO or on
     the PRMS/CTO Website at http://www.unmc.edu/ccto/.



VII. PROTOCOL TERMINATION and CONCLUSION of DSMC REVIEW

     Principal investigators are responsible for notifying the DSMC of protocol termination, irrespective of
     the reason for termination. Notification should be made directly to the UECC CTO Office (ECI, Rooms
     5003) or via campus mail (UNMC zip 6805).
     Review of the protocol, scheduled review of AE‟s and real time review of SAE‟s by the DSMC will
     continue for as long as research subjects are considered to be at risk for protocol associated toxicity.


VIII. REVIEW PROCEDURES

     A. ASSIGNMENT OF REVIEWERS
        Protocols, AE Reports and SAE‟s scheduled for review are assigned to one of the DSMC
        members by the DSMC administrator. DSMC members can not review protocols, AE Reports and
        SAE‟s if they are a principal or secondary investigator on that protocol.

         New protocols and changes to a previously reviewed protocol will be reviewed by all members
         who are eligible to review the protocol and who are attending the meeting during which the
         protocol is reviewed. Scheduled AE reports and SAE reviews will be reviewed by a single
         member in attendance at the meeting during which the AE Report or SAE is reviewed.

         If expedited review of a SAE is required, the DSMC Chair may assign the review to a member of
         the DSMC or conduct the review himself/herself. In either case, the outcome of the expedited
         review must be confirmed by the full DSMC at its next regularly scheduled meeting.
DSMC Policies and Procedures                                                             Page 33 of 74

     B. CONFLICT OF INTEREST POLICY
        Protocols, AE‟s and SAE‟s can not be reviewed by DSMC members who function as principal or
        secondary investigator on that protocol. DSMC members are expected to recluse themselves from
        the discussion and voting on protocols, AE Reports and SAE‟s on which they serve as an principal
        or secondary investigator.

         In addition, DSMC members will recluse themselves from discussion and voting in case they have
         another conflict of interest (personal, financial, ethical) for the protocol, AE Report or SAE under
         review. One of the DSMC members will temporarily replace the Chair if the Chair has to recluse
         himself/herself to avoid a conflict of interest.

     C. REVIEW OUTCOMES
        1. Review of New Protocol and/or Changes: New protocol reviews or reviews of changes to
            previously reviewed paragraphs pertaining to Adverse Event Reporting Guidelines and
            Toxicity (Section 9 in the UECC SRC protocol format): The results of review of the protocol
            (including recommendations for change) will be communicated to PI in writing. The results
            will also be reported the SRC and the SRC will incorporate these observations into the SRC
            review process.
         2.    Review of AE’s and SAE’s: Regularly scheduled review of AE reports and review of
               serious adverse events can result in the following outcomes:
                    No protocol and/or operational changes required: The investigator will be notified
                     in writing with a copy to the SRC and the IRB.
                    Additional information required: The information can be requested directly from the
                     investigator or through the Audit Committee. The investigator will be notified in writing
                     with copies to the SRC, the IRB and the Audit Committee.
                    Minor protocol and/or operational changes recommended: The investigator will be
                     notified in writing with a copy to the SRC and the IRB.
                    Major protocol and/or operational changes recommended: This recommendation
                     will generally result from the identification of significant concerns for the safety of
                     research participants by the DSMC. The investigator, the Chair of the SRC and the
                     Associate Director for Clinical Research will be notified immediately both verbally and
                     in writing about the DSMC concerns, with a copy to the IRB. The SRC and/or the
                     Associate Director for Clinical Research may decide to temporarily suspend accrual to
                     the protocol pending acceptable changes.

     D. VOTING PROCEDURES
        A formal vote is required whenever major protocol changes are recommended. In addition, the
        DSMC Chair can request a formal vote on all other proposals, including proposals to change
        procedures, etc. Decisions are made by a simple majority of votes cast by those present.
UECC SRC Protocol Format                                                                                                   Page 34 of 74



                            APPENDIX A.1: DSMC Report for Phase I Protocols
IRB#:                      PI:
TITLE:
Study coordinator/contact:                                 Phone:                    Email:
E-mail address of individual responsible for report:
Protocol Status:                 protocol open to accrual
                                 protocol closed to accrual, patients under treatment
                                 protocol closed to accrual, no further patient treatment (Final Report)
Date of last DSMC review:                                 # of new patients enrolled since last DSMC review:
Report current as of (date):                              total # of patients enrolled on study:
FOR MULTI PHASE STUDIES: Has an interim report been completed?            Yes                                                 No
If yes, please include a copy of the interim report with this submission.
INSTRUCTIONS:
1) Provide the following information separately for each dose level studied:
   Note: For non-UNMC coordinated Multi-Center Institutional studies (Protocol in which a local PI is
   participating in a study that is designed and developed at another institution) include only information
   on UNMC/Eppley Cancer Center treated patients.
     1.    Dose and schedule of agent(s)
     2.    Total number of patients entered at that dose/schedule
     3.    Total number withdrawn without receiving treatment
     4.    Total number found to be ineligible for protocol
2) Complete and attach an Adverse Event Reporting Worksheet, listing all reportable adverse events (as
   detailed in Section 9.0 of the protocol document). Worksheet must include:
     1. The patient‟s UNMC medical record number or unique protocol identification number (if no UNMC
        MR# is available)
     2. A Short Description of the type of adverse/serious adverse event (AE/SAE), using an asterisk (*)
        to mark any events that were not reported on previous Adverse Event Reporting Worksheets
     3. The Date of the AE/SAE
     4. The Grade of the AE/SAE (see CTC v3.0 for definitions)
     5. The Attribution of the AE/SAE (unlikely, possibly, probably or definitely related to treatment)
     6. For all AE/SAE's that were not reported on previous Adverse Event Reporting Worksheets, an
        indication of whether the AE/SAE was serious or not serious

PI Signature & Date: __________________________________________________________




UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office               Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                                        Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                                     Fax: (402) 559-4970
  Continuing Review Submission Form for Institutional, Industry and Other Peer Reviewed Studies (Version 02/10/2010)          Page 34 of 74
DSMC Policies and Procedures                                                                Page 35 of 74


         APPENDIX A.2: DSMC Report for Pilot, Phase II and Phase III Studies
                    DSMC Report for Pilot, Phase II and Phase III Protocols
IRB#:                PI:
TITLE:
Study coordinator/contact:                  Phone:           Email:
E-mail address of individual responsible for report:
Protocol Status:           protocol open to accrual
                           protocol closed to accrual, patients under treatment
                           protocol closed to accrual, no further patient treatment (Final Report)
Date of last DSMC review:                    # of new patients enrolled since last DSMC review:
Report current as of (date):                 total # of patients enrolled on study:
FOR MULTI PHASE STUDIES: Has an interim report been completed?            Yes                  No
If yes, please include a copy of the interim report with this submission.

INSTRUCTIONS:

1. Provide the following information:
   Note: For non-UNMC coordinated Multi-Center Institutional studies (Protocol in which a local PI is
   participating in a study that is designed and developed at another institution) include only information
   on UNMC/Eppley Cancer Center treated patients.
    1. Total number of patients entered
    2. Total number withdrawn without receiving treatment
    3. Total number found to be ineligible for protocol

2. Complete and attach an Adverse Event Reporting Worksheet, listing all reportable adverse events (as
   detailed in Section 9.0 of the protocol document). Worksheet must include:
   1. The patient‟s UNMC medical record number or unique protocol identification number (if no UNMC
      MR# is available)
   2. A Short Description of the type of adverse/serious adverse event (AE/SAE), using an asterisk (*) to
      mark any events that were not reported on previous Adverse Event Reporting Worksheets
   3. The Date of the AE/SAE
   4. The Grade of the AE/SAE (see CTC v3.0 for definitions)
   5. The Attribution of the AE/SAE (unlikely, possibly, probably or definitely related to treatment)
   6. For all AE/SAE's that were not reported on previous Adverse Event Reporting Worksheets, an
      indication of whether the AE/SAE was serious or not serious

PI Signature & Date: __________________________________________________________
DSMC Policies and Procedures                                      Page 36 of 74


                    APPENDIX A.3: Adverse Event Reporting Worksheet
DSMC Policies and Procedures                                                             Page 37 of 74



APPENDIX B: SRC SUBMISSION REQUIREMENTS: (Please submit in order listed below)
NOTE: “If applicable” is defined as a document that is not required, but should be submitted if it is
available and/or has been changed from the previous submission.

New Protocols
1. SRC New Protocol Form – required
2. Copy of IRB application – required
3. Consent form(s) (if applicable)
4. Data collection forms
   a. Investigator Initiated – required
   b. All Other – not required
5. Investigator Brochure (if applicable)
6. Grant application (if applicable) - SRC may request a copy of the entire grant if the protocol is not
   sufficiently detailed to allow evaluation of the science
7. Protocol, including version and date
   a. Investigator Initiated (therapeutic, chemoprevention and ancillary) – SRC format required
   b. National Cooperative Groups – SRC format not required (may be submitted without conversion to
        SRC format)
   c. Correlative (lab based) – SRC format not required (IRB application usually sufficient)
   d. Therapeutic Pilot – SRC format required
   e. Non-Therapeutic Pilot - SRC format not required (IRB application plus statistical section usually
        sufficient)

Continuing Review
1. SRC Continuing Review Submission From – required
2. Copy of Revised IRB application – required
3. Copy of Consent form – required
4. Copy of Progress Report/Publications (if applicable)

Change (Investigator-Initiated, Multi-Center, Industrial Only)
1. SRC Request for Change Submission Form – required
2.   Copy of any correspondence related to this change (if applicable)
3.   Copy of the IRB Request for Change form (if applicable)
4.   Copy of Section II from the IRB Biomedical application (if applicable)
5.   Copy of the revised consent form (if applicable)
6.   Copy of revised data collection form (if applicable)
7.   Copy of revised Investigator‟s Brochure (if applicable)
8.   Copy of the revised protocol (if applicable)

Change (National Cooperative Group)
1. Nothing – beginning January 2007, SRC no longer reviews changes to National Cooperative Group trials
UECC SRC Protocol Format                                                                                                   Page 38 of 74



                                 APPENDIX C: UECC SRC PROTOCOL FORMAT
        Protocol Format
        NIH designated Clinical Cancer Centers must conduct scientific peer review of clinical protocols. A
        standardized protocol format is used for the successful implementation of this process. All UECC
        Investigator-initiated protocols developed at this institution involving clinical research shall include the
        following elements or the equivalent:

           Title Page
           Abstract (no more than 250 words)
           Schema
           Section 1.0   Objectives
           Section 2.0   Introduction, which includes background data and future aims
           Section 3.0   Eligibility criteria
           Section 4.0   Randomization/registration procedures
           Section 5.0   Treatment plan or research design
           Section 6.0   Measurement of effect
           Section 7.0   Study parameters
           Section 8.0   Drug formulation and procurement
           Section 9.0   Toxicity and adverse event reporting guidelines
           Section 10.0 Biostatistical considerations including stopping criteria
           Section 11.0 Records to be kept
           Section 12.0 Patient consent form statement
           Section 13.0 References
           Section 14.0 Data collection forms (The SRC may withhold review and approval of a new
                         Investigator-initiated institutional protocol until all data collection forms are
                         submitted and reviewed).

        This standard format is expanded in greater detail in the following pages.




UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office               Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                                        Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                                     Fax: (402) 559-4970
  Continuing Review Submission Form for Institutional, Industry and Other Peer Reviewed Studies (Version 02/10/2010)          Page 38 of 74
UECC SRC Protocol Format                                                                  Page 39 of 74


      Abstract: Describe the purpose, specific aims, hypothesis, conceptual framework (if applicable),
      methods (design, sample size, eligibility, instruments, procedures, data analysis) and outcome
      implications for research and practice.

      Schema: This should be a diagrammatic representation of the study if possible. The schema should
      include the main details of the study.

      Section 1.0 Objectives: The objectives of the research study should be stated clearly. The study
      design should be capable of answering the questions posed by the objectives. The statistical/data
      analysis section should clearly state how the data will be analyzed in relation to each of the study‟s
      objectives. Specific requirements of therapeutic studies are discussed below.

          Phase I therapeutic studies Phase I trials determine a safe method/dose for Phase II trials and
             define acute effects that occur with a relatively high frequency in normal tissues. In addition,
             these trials may examine the agent‟s pharmacology and may reveal evidence of anti-tumor
             activity. Therapeutic intent is always present in Phase I trials; anticancer drugs are usually
             not tested in patients unless preclinical activity studies have already demonstrated evidence
             of significant activity in lab models. The initial starting dose in humans must be justified in
             the protocol. The initial dose may be increased gradually by some defined procedure until a
             level is found which produces limiting, but tolerable toxicity and/or clear signs of therapeutic
             activity.

          Phase II therapeutic studies A Phase II study determines a) whether a treatment/agent
             has anti-tumor activity and b) estimates the response rate in a defined patient population.
             Well-designed Phase II trials do not permit the entry of more patients than necessary to
             ensure the presence or absence of a clinically significant level of activity. Because various
             tumor types have different prognostic factors, eligibility requirements, and patterns of
             responsiveness to a particular drug or combination of drugs or therapy, Phase II trials are
             conducted in homogenous clinical entities (i.e., metastatic breast cancer patients with
             measurable disease and a normal or near normal performance status).

          Phase III therapeutic studies If significant activity is observed in any disease during Phase II
             testing, subsequent clinical trials usually compare the new drug or treatment modality with
             standard treatment or observation, if no standard treatment exists. Relevant endpoints (i.e.,
             time to progression, survival, quality of life) must be used to measure benefit.

          Pilot Projects The primary objective is to collect preliminary data to plan a future protocol. The
              trial must be limited in duration and the investigator must specify future plans. The
              purpose(s) may be to test the feasibility of the study in a given population; to evaluate
              whether the instruments are sensitive to change; or to assess the ability to recruit for the
              study. In these cases, no control group is necessary. Endpoints such as the proportion of
              eligible subjects who consent to be randomized are appropriate as a standard control group.
UECC SRC Protocol Format                                                                    Page 40 of 74


      Section 2.0 Introduction: Sufficient referenced background information should be included so that
      the rationale for the study is clear. For example, previous work done in animals and humans should
      be cited. Any unpublished data relevant to the rationale should be included. Toxicology studies
      carried out prior to Phase I trials that provide the investigator with a) estimates of a starting dose for
      clinical trials and b) prediction of the likely effects of the drug on normal tissues should be included.

      Section 3.0 Eligibility Criteria: This should be a specific listing of all criteria necessary to be met for
      a subject to be eligible for the given study. Written informed consent must be an eligibility
      requirement. Types of subjects (minors, fetuses, pregnant women, etc.) should be specified. Many
      studies also include a section of exclusion criteria. Psychological, familial, sociological, or
      geographical conditions which do not permit compliance with the study should be considered.
      Studies with objective response as an endpoint should include clear statements specifying whether
      tumor sites to be followed for response must be measurable, what criteria must be fulfilled to
      consider disease measurable, whether evaluable disease is permitted, and if so, at what sites.
      Specific elements for Phase I-III studies are described below.

          Phase I Trials. Patients eligible for Phase I studies generally must have confirmed
             malignant disease which is not amenable to conventional forms of therapy or for which there
             is no standard effective treatment. Patients should have normal or near normal organ
             function in order that the investigator may reliably distinguish drug effects from disease
             effects. When there is impairment of a major organ, drug treatment may produce increased
             toxicity because of decreased clearance or additive injury to the organ. Since most cancer
             drugs will ultimately be used in some patients having impairment of major organ function
             (particularly cardiac, hepatic, and renal), it is sometimes reasonable to explore their use in
             such patients through Phase I trials explicitly designed to determine safe doses and
             pharmacology in these settings.

          Phase II and III Trials. Elements to be considered include histological confirmation of disease,
             stage, prior therapy, measurable vs. evaluable disease, age, sex, performance status, life
             expectancy, and organ function requirements. For the treatment of diseases for which highly
             effective systemic therapy is not available (e.g. carcinomas of the large bowel, kidney, liver,
             pancreas, and malignant melanoma), Phase II or III studies may be limited to patients with
             no prior chemotherapy. For diseases in which chemotherapy may cause frequent objective
             regressions with or without survival benefit, Phase II or III studies may or may not be
             restricted to patients with no prior therapy. For diseases which are potentially curable with
             systemic treatment (e.g. acute leukemia, diffuse NHL, Hodgkin‟s disease, testicular cancer,
             limited small cell lung cancer, and ovarian cancer), Phase II or III studies generally enroll
             patients who have had the minimum extent of prior treatment compatible with current ethical
             standards of care.

          Examples of specific criteria for eligibility.
                  Histologically confirmed cancer (residual, recurrent, or metastatic)
                  Adequate hepatic, renal, and bone marrow function: Billirubin <1.5 mg%, AST less
                          than five times the upper limits of normal, creatinine <1.5 mg%, etc.
                  Patient must have measurable or evaluable disease (depending on protocol).
                  Patient must be inoperable with no other definitive therapy available.
UECC SRC Protocol Format                                                                  Page 41 of 74


          Examples of specific criteria for exclusion.
                  Prior therapy with drugs to be used in the proposed study.
                  Disease process which might be adversely affected by a particular drug (e.g.,
                           congestive heart failure with Doxorubicin)
                  Patients with acute intercurrent complications such as infection or post surgical
                           complications
                  Patients below a certain age or with a poor performance status as defined by a
                           standard performance scale.
                  Patients with a history of a second malignancy.

      Section 4.0 Registration Procedure: The date of enrollment should be clearly defined as either the
      date of consent or as the date of the first protocol related intervention.
      Procedures for subject entry (e.g., randomized or non-randomized) should be specified. If the
      Protocol is randomized, required information includes who will be performing randomization and their
      contact information and the subject characteristics and stratification factors (if any) to be provided at
      the time of entry. For non-randomized studies, the procedure for screening and recording patient
      eligibility for the study should be described.

      For multi-center studies headquartered at the UNMC Eppley Cancer Center, it is important that this
      section clearly state who is authorized to register and screen patients and the pertinent phone
      numbers and location of the office, hours of operation, and what information will be required. For
      studies involving the processing of lab samples, this section should contain information on how the
      specimens are to be processed and shipped (i.e., on ice, by what carrier, etc.), what accompanying
      referral forms are required, to whom samples should be sent, and hours for receipt of specimens.

      Section 5.0 Treatment Plan of Research Design: This section will vary depending on the nature of
      the clinical trial. The following examples are given for a drug treatment program.

          Administration Schedule:
             Description of various treatments including dose and schedule of all drugs used.

          Dose Modifications
                  Define criteria for dose modification
                  Define criteria for holding and resuming treatment.
                  Define criteria for termination of treatment.

          Duration of Therapy
                   Define criteria for stopping therapy. For example, disease progression or evidence of
                           unacceptable drug toxicity.
                   Define duration of therapy for patients with stable disease.
                   Define duration of therapy for responding patients.
                   Define stopping rules for the entire study. If certain target(s) are reached see Section
                           10.

          When applicable consider recommendations for supportive care.

      Section 6.0 Measurement of Effect: In this section the parameters (e.g., response, time to
      progression, survival) for assessing the effect of an intervention are defined. Each protocol will
UECC SRC Protocol Format                                                                    Page 42 of 74


      specifically define these endpoints. Response (e.g., complete response, partial response, stable
      disease, and progressive disease) should be defined. For all Investigator-initiated protocol
      evaluating tumor response in solid tumors, the SRC expects that Response Evaluation Criteria in
      Solid Tumors (RECIST) (http://ctep.cancer.gov/guidelines/recist.html) will be used to monitor
      treatment response unless the PI provides justification for the use of other criteria. The extent of the
      restaging that is required to document a complete response must be defined. The protocol should
      state who will provide oversight on response evaluation (i.e., the principal investigator or a
      designated review committee).

      Section 7.0 Study Parameters: Study parameters are best presented in tabular form indicating tests
      and frequency of measurements (see below). The following guidelines might be used for prestudy
      testing to determine eligibility requirements in advanced disease protocols: all baseline
      x-rays (CT, MRI, bone scans, SCR) should be obtained within four weeks of the planned initiation of
      treatment; and CBC with differential, liver function studies and chemistries shall be done within one
      week of initiation of treatment protocol.

       Test                                Prior to   Weekly        Before Each Drug        Every 3
                                           Testing                  Administration          Months
       History and Physical Exam
       Measurement of Tumor
       Performance Status
       Hemoglobin & HCT, WBC
       w/diff,
       platelet count, BUN, serum
       creatinine, Glucose, bilirubin,
       alkaline, Phosphatase, SGOT

      Section 8.0 Drug Formulation and Procurement: Pharmaceutical trials should contain a section for
      each drug or biologic agent and dose form, its preparation, dilution, stability, method of administration
      precautions, and known clinical toxicities. The supplier of each drug and information about
      commercial availability should also be specified.

      Section 9.0 Toxicity and Adverse Event Reporting Guidelines: All investigator-initiated protocol
      shall include a definition of adverse events specific to the protocol. Therapeutic (i.e. disease related)
      protocol shall adhere to institutional, FDA, and CTEP guidelines for toxicity and adverse event
      reporting (CTE Common Toxicity Criteria can be obtained through the UNMC Eppley Cancer Center
      PRMS office or at http://ctep.info.nih.gov/CT3/ctc.htm). The Data and Safety Monitoring Committee
      (DSMC) monitors all internal toxicities and adverse events that occur on Investigator-Initiated
      protocol, and provides a monthly report to the SRC on its review. See Appendix D for a more
      complete description of the DSMC. With the exception of transplant protocol that are investigator-
      initiated, all internal serious adverse events (expected or unexpected, regardless of attribution) must
      be reported to the DSMC. For transplant protocols, the DSMC recognizes that certain toxicities are
      routinely anticipated. The investigator can indicate that a particular toxicity is anticipated for the vast
      majority of research participants and that such toxicity will therefore not be reported. The DSMC will
      determine in its initial review of the protocol if such exclusion from standard reporting guidelines is
      acceptable.
UECC SRC Protocol Format                                                                      Page 43 of 74


      Section 10.0 Statistical Considerations: Each protocol should be developed and discussed with a
      biostatistician prior to submission. Meaningful biostatistical design of clinical trials is facilitated if the
      biostatistician understands the background of the disease being studied such as its natural history as
      well as its history using current treatments. This section should address how each objective will be
      assessed with the criteria for statistical significance stated. The following issues shall be discussed:
      definition of analysis population, determination of sample size, estimated duration of study, accrual
      goal, method of analyses, criteria for stopping the trial earlier than planned. Possible reasons for
      stopping a trial early may include but are not limited to unacceptable toxicities, the trial appears
      unlikely to succeed either because of poor accrual, high dropout rates, etc., early results effectively
      answer the study question either positively or negatively, and it becomes unnecessary (and possibly
      unethical) to continue the study.

      The principal investigator (PI) should provide 1) the endpoints of the study such as response rate,
      toxicity, disease-free survival or overall survival, and 2) patient characteristics that affect response of
      the disease under consideration such as performance status, extent of disease, prior therapy,
      metastatic sites, etc.

      The PI and biostatistician should consider sources of patient accrual such as other centers and
      „feeder‟ trials (i.e., ones with higher priority) available to determine expected accrual rates. The
      diseases being studied and ethical questions present in the treatment of these diseases can
      influence the choice of experimental design such as single stage, multiple stage, or crossover;
      therefore, a discussion between the PI and the biostatistician should include these considerations as
      well (more specific requirements can be broken down by the type of trial):

      Pilot: While statistical justification of sample size need not be included, estimated duration of study,
      method of analyses, decision-making criteria, estimated accrual per year and criteria for stopping the
      trial earlier than planned should be addressed. Statistical justification of sample size might include a
      power analysis to determine the size of the pilot sample based on what will be needed for the larger,
      future study‟s sample.

      Phase I: The PI must provide an estimate of the number of patients to be accrued per year. Sample
      size is determined by results as the trial proceeds. A sample size of 15 – 24 patients is not unusual.
      Phase I trials may require more patients per dose level depending on the biologic endpoint being
      measured. If a dose escalation is planned, then dose escalation plan, definition of dose limiting
      toxicity, and definition of maximum tolerated dose (or dose to be taken to subsequent evaluation for
      non-anti-neoplastic agents) must be specified. For phase I trials without a dose escalation, the
      primary safety endpoint must be specified along with acceptable and unacceptable rates for its
      incidence and corresponding stopping rules.

      Phase II and III Requirements:
       A. Estimation of the number of patients that can be accrued per year;
       B. Estimation of the percent of accrued patients that will be fully evaluable,
           False positive error (recommending an ineffective agent for further study). This error is usually
               .05.
           False negative error (declaring an effective agent as ineffective). Typical values are
               .10 or .20.
       C. One sample design (i.e., no randomization into two or more treatment groups),
           1. Is there a standard treatment with known response rates?
UECC SRC Protocol Format                                                                  Page 44 of 74


                        If yes, what is the proportion of response of the standard treatment?
                        If no, what is the accuracy needed in estimating the proportion of response (i.e., .30
                           + .05)?
            2. Is there a threshold value or proportion responding above which the agent being tested is
                  deemed a good candidate for Phase III testing? If yes, what is that proportion (i.e., .20 or
                  .30)?
        D. Two sample design (i.e., randomization into two treatment groups).
             If two success rates are to be compared:
                        What is the success rate of the control?
                        What is the expected success rate of the treatment?
           Is there a threshold value or proportion responding above which the agent being tested is
                deemed a good candidate for Phase III testing? If yes, what is that proportion (i.e., .20 or
                .30)?
                         What is the expected outcome of the control groups?
                         What is the expected outcome of the treatment group?

      Section 11.0 Records to be Kept: A list of all records, including flow sheets, data collection
      forms/instruments, summary and evaluation forms should be compiled. A description of where and
      how these records will be maintained needs to be included to facilitate retrieval by various audit
      committees. This includes where and how laboratory and diagnostic studies will be retrieved or
      duplicated as part of the records for all subjects. The Biostatistics Shared Resource is available to
      assist the investigator in the development of a research database.

      Section 12.0 Patient Consent: The consent form should adhere to the guidelines established by the
      Institutional Review Board of the University of Nebraska Medical Center.

      Section 13.0 References

      Section 14.0 Data Collection Forms: All Investigator-initiated data collection forms must be
      submitted when the protocol is initially reviewed. Assistance in preparing data collection forms for
      reporting data may be obtained from the Biostatistics Shared Resource. The SRC may withhold
      review and approval if data collection forms are not submitted with the protoc
                          APPENDIX D.1: NEW PROTOCOL SUBMISSION FORM

Instructions: Please complete and submit this form to the UNMC Eppley Cancer Center Protocol Review and
Monitoring System (PRMS) Office (Campus Zip 6805) by the fourth Friday of each month. Submissions received after
this deadline will be reviewed at the subsequent SRC meeting. NOTE: In 2010, the submission deadline is the 3rd
Friday in February (02/19/10), and the 4th Wednesday in November and December (11/24/10 and 12/22/10).

SECTION I: BASIC PROTOCOL DATA
Current IRB#:
Title:
PI:                                                    Phone:                          Email:
Study Coordinator/Contact:                             Phone:                          Email:


Is this a re-submission of a previously tabled protocol?                        Yes        No
NOTE: Tabled protocols must be resubmitted in their entirety.

SECTION II:         Check here if you believe this protocol qualifies for SRC EXPEDITED REVIEW (previously called
               SRC Exempt).
      NOTE: Many specimen studies, medical record reviews, and projects involving existing documents or records
      may qualify for “SRC Expedited Review”. Some examples of SRC Expedited Review research include:
       Anonymous surveys and retrospective chart reviews
       Analysis of discarded pathological specimens without personal identifiers
       Proposals involving previously banked materials and/or tissues
       Protocols to obtain tissue or other biological samples for prospective or undetermined future research

SECTION III: SRC CLASSIFICATION – Please identify the Classification that best matches this protocol .

      A. INVESTIGATOR-INITIATED INSTITUTIONAL TRIAL: Protocol that has been designed and developed by a
         local investigator. Protocol may be implemented only at UNMC or at multiple clinical sites. Protocol may or
         may not have received external funding and may include collaborative studies conducted with industry in which
         the local PI is the primary contributor to the design, implementation and monitoring of the trial.
              Single-Site Trial: Protocol being implemented by local PI at UNMC/Nebraska Medical Center only.
              Multi-Site Trial: Protocol being implemented by local PI at more than one clinical site.
              Site(s) where trial will be implemented:
              Industry-Supported Trial: Protocol that is receiving some funding from industry.
              Grant-Funded Trial: Protocol that has been externally peer reviewed for funding purposes only
               NOTE: If the protocol is part of a grant submission and is not sufficiently detailed to allow evaluation of the
               science, the SRC may request a copy of the entire grant. Please attach a copy of the entire grant if you
               believe this will aid the SRC in its review.
               Grant Funding Source:
               Grant Number:       Anticipated Grant Submission Date:

UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office         Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                                  Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                               Fax: (402) 559-4970
  New Project Submission Form (Version 02/10/2010)                                                                      Page 45 of 74
    B. MULTI-CENTER INSTITUTIONAL TRIAL: Protocol in which a local PI is participating in a study that is
       designed and developed at another institution and where more than one IRB approval is required.

    C. NATIONAL COOPERATIVE GROUP TRIAL: Protocol that is initiated by an NCI funded study group and
       receives CTEP review. NOTE: Only those study groups listed below qualify for this classification.
           ACRIN            CALGB         ECOG                  GOG              NSABP                RTOG
           ACSOG            COG           EORTC                 NCICA            NCCTG                SWOG
         Did you as investigator play a major role in the development of this protocol?                No         Yes
         If yes, please explain your level of participation.

    D. INDUSTRIAL TRIAL: Protocol that is designed, developed and monitored by Industry.
         Did you as investigator play a major role in the development of this protocol?                No         Yes
         If YES, please explain your level of participation.

    E. OTHER EXTERNALLY PEER-REVIEWED TRIAL: R01, P01 or other trial funded by NIH or supported by other
       peer-reviewed funding organizations, such as the ACS, the Komen Foundation, Leukemia and lymphoma
       Society, U.S. Army (DOD) etc.
         Did you as investigator play a major role in the development of this protocol?                No         Yes
         If YES, please explain your level of participation.


SECTION IV: NCI CLASSIFICATION and PHASE (for intervention trials) or TYPE (for non-intervention trials)

    A. THERAPEUTIC INTERVENTION TRIAL: Clinical trial with therapeutic intent using an agent or device (e.g.
       drugs, radiation, surgery, and/or biological agents).

    B. PREVENTION INTERVENTION TRIAL: Clinical trial for the modulation of cancer risk and inhibition of cancer
       progression using behavioral modification, nutrition, dietary or chemoprevention interventions.

         1. PHASE: For either (A) Therapeutic or (B) Prevention Intervention Trials, please indicate the study PHASE.
               Pilot or Feasibility: Protocols where primary objective is to collect preliminary data to plan a future
               protocol. The trial must be limited in duration and the investigator must specify future plans.
               Phase I: Protocols designed to determine a safe method/dose for Phase II trials and define acute
               effects that occur with a relatively high frequency in normal tissues.
               Phase II: Protocols designed to a) determine whether a treatment/agent has anti-tumor activity and
               b) estimate the response rate in a defined patient population.
               Phase III: Protocols designed to compare the new drug or treatment modality with standard
               treatment or observation, if no standard treatment exists.
               Phase IV: Protocols designed to evaluate side effects that were not apparent in Phase III trials after
               a treatment has been approved and is being marketed.
               Combination:        Phase I/II         Other: Please specify


UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office   Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                            Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                         Fax: (402) 559-4970
  New Project Submission Form (Version 02/10/2010)                                                                Page 46 of 74
    C. NON-INTERVENTION TRIAL: 1) Epidemiologic, outcome, or other observational study; or 2) study
       associated with a clinical trial or other biological study using clinical specimens that can be linked to individual
       patient or participant data.

         1. TYPE: For Non-Intervention Trials, please indicate the study TYPE.
               Screening, Early Detection, or Diagnostic Trial: Protocol designed to test the efficacy of devices,
               techniques, procedures, or tests for earlier/more accurate detection or diagnosis of disease.
                   Supportive Care Trial: Protocol designed to improve the comfort and quality of life for the patient.
                   Epidemiologic/Observational Trial: Study among cancer patients and healthy populations that
                   involve no intervention or alteration in the status of the participants (e.g., surveillance, risk
                   assessment, environmental and behavioral studies, etc.)
                   Ancillary or Companion Trial: Auxiliary study that is stimulated by, but not a required part of, a
                   main clinical trail, and that utilizes patient or other resources of the main trial to generate information
                   relevant to it.
                   NOTE: Companion or ancillary studies must be linked to an active trial, or epidemiologic or other
                   observational study (screening, early detection, diagnostic; therapeutic; or prevention) and should
                   include only patients accrued to that trial or study.
                   Correlative Trial: Laboratory based study using specimens to assess cancer risk, clinical outcomes,
                   response to therapies, etc.
                   NOTE: Correlative studies must be linkable to other patient data.


SECTION V: Please indicate 1) whether this protocol is a transplant protocol; 2) if it involves randomized
treatment or an investigational drug; and 3) if it is intended for newly diagnosed or relapsed subjects, or both.

Transplant Protocol:                  Yes            No
Randomized Treatment:                 Yes            No
Investigational Drug:                 Yes            No
Intended Subjects:                    Newly Diagnosed                Relapsed     Both Newly Diagnosed and Relapsed


SECTION VI: Please identify the tumor type/s and/or anatomic site/s the protocol addresses.

    Ancillary                                             Genitourinary                              Multiple Myeloma
    Brain and Neuro                                       GVHD                                       MDS
    Breast                                                GYN - Other                                Ovarian
    Cervical                                              Head/Neck                                  Pancreatic
    Colorectal                                            Hepatocellular                             Prostate
    Endocrine                                             Leukemia                                   Sarcoma
    Endometrial                                           Lung                                       Other
    Esophageal                                            Lymphoma                                   Please Specify:
    GI - Other                                            Melanoma/Skin


UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office   Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                            Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                         Fax: (402) 559-4970
  New Project Submission Form (Version 02/10/2010)                                                                Page 47 of 74
   SECTION VII: Does this protocol compete with other ongoing studies?                          Yes       No

   If YES, please list any competing protocols (i.e. those with similar eligibility criteria) and rank them in the order of
   priority that they would be offered to the patient (i.e. #1, #2).
   NOTE: Per NCI Guidelines, protocols must be ranked in the following order of priority: 1) Investigator-Initiated
   Institutional trials; 2) Multi-Center Institutional trials; 3) National Cooperative Group trials; 4) Industry trials; and 5)
   Other Externally Peer Reviewed trials. A list of active protocols is available from the UNMC Eppley Cancer Center
   PRMS office or on their web site at http://www.unmc.edu/ccto/.
   Rank      IRB #        Protocol Classification                                                Title
                         (Investigator-Initiated, Multi-
                        Center, National Cooperative
                          Group, Industrial or Other
                         Externally Peer Reviewed)




SECTION VIII: ACCRUAL PROJECTION, INFORMATION and REPORTING:

   A. During the NEXT 12 MONTHS:
   1. What is the targeted accrual for the entire study, including all participating sites?
   2. What is the targeted accrual at UNMC/The Nebraska Medical Center?

   B. During the DURATION OF THE STUDY:
   1. What is the targeted accrual for the entire study, including all participating sites?
   2. What is the targeted accrual at UNMC/The Nebraska Medical Center?
   3. What is the targeted number of years this study will remain active?

   C. ACCRUAL REPORTING REQUIREMENTS:

           I agree to submit copies of the consent forms for each subject registered to this protocol to the UNMC Eppley
           Cancer Center PRMS Office (Campus Zip 6805) within one week of enrollment.




   UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office   Eppley Science Hall (ESH) Room 10006 and 10007
   986805 Nebraska Medical Center                                                                            Phone: (402) 559-4969
   Omaha NE 68198-6805                                                                                         Fax: (402) 559-4970
     New Project Submission Form (Version 02/10/2010)                                                       Page 48 of 74
SECTION IX: New Protocol Submission Checklist (please mark all that apply and submit in order listed)
         Original Signed and Dated SRC New Protocol Submission Form - required
         Cover letter and/or copy of relevant correspondence (if applicable)
         Copy of the IRB Application for Biomedical Research form, Sections I and II - required
         Consent form/s (if applicable)
         Data collection form/s (if applicable) - required for all Investigator-Initiated trials
         Investigator Brochure (if applicable)
         Grant application (if applicable)
         Protocol with version and date clearly marked on the face page

         NOTE: A protocol in SRC format is required for all Investigator-Initiated and Therapeutic Intervention Pilot trials.
         Instructions on preparing a protocol in SRC format are available from the UNMC Eppley Cancer Center PRMS
         office or on their web site at http://www.unmc.edu/ccto/.


    ___________________________________                                             ________________
        Signature of Principal Investigator                                                Date




    UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office         Eppley Science Hall (ESH) Room 10006 and 10007
    986805 Nebraska Medical Center                                                                                  Phone: (402) 559-4969
    Omaha NE 68198-6805                                                                                               Fax: (402) 559-4970
      New Project Submission Form (Version 02/10/2010)                                                             Page 49 of 74
                          APPENDIX D.2: NEW PROTOCOL SUBMISSION FORM
           For Trials to be Opened ONLY at Children's Hospital and Medical Center (Children's)

Instructions: Please complete and submit this form to the UNMC Eppley Cancer Center Protocol Review and
Monitoring System (PRMS) Office (Campus Zip 6805) by the fourth Friday of each month. Submissions received after
this deadline will be reviewed at the subsequent SRC meeting. NOTE: In 2010, the submission deadline is the 3rd
Friday in February (02/19/10), and the 4th Wednesday in November and December (11/24/10 and 12/22/10).

SECTION I: BASIC PROTOCOL DATA
Current IRB#:                                           Previous Children's IRB #:
Title:
PI:                                                     Phone:                         Email:
Study Coordinator/Contact:                              Phone:                         Email:
Is this a re-submission of a previously tabled protocol?                        Yes        No
NOTE: Tabled protocols must be resubmitted in their entirety.

SECTION II:         Check here if you believe this protocol qualifies for SRC EXPEDITED REVIEW (previously called
               SRC Exempt).
      NOTE: Many specimen studies, medical record reviews, and projects involving existing documents or records
      may qualify for “SRC Expedited Review”. Some examples of SRC Expedited Review research include:
       Anonymous surveys and retrospective chart reviews
       Analysis of discarded pathological specimens without personal identifiers
       Proposals involving previously banked materials and/or tissues
       Protocols to obtain tissue or other biological samples for prospective or undetermined future research


SECTION III: SRC CLASSIFICATION – Please identify the Classification that best matches this protocol .

      A. INVESTIGATOR-INITIATED INSTITUTIONAL TRIAL: Protocol that has been designed and developed by a
         local investigator. Protocol may be implemented only at UNMC or at multiple clinical sites. Protocol may or
         may not have received external funding and may include collaborative studies conducted with industry in which
         the local PI is the primary contributor to the design, implementation and monitoring of the trial.
              Single-Site Trial: Protocol being implemented by local PI at UNMC/Nebraska Medical Center only.
              Multi-Site Trial: Protocol being implemented by local PI at more than one clinical site.
              Site(s) where trial will be implemented:
              Industry-Supported Trial: Protocol that is receiving some funding from industry.
              Grant-Funded Trial: Protocol that has been externally peer reviewed for funding purposes only
               NOTE: If the protocol is part of a grant submission and is not sufficiently detailed to allow evaluation of the
               science, the SRC may request a copy of the entire grant. Please attach a copy of the entire grant if you
               believe this will aid the SRC in its review.
               Grant Funding Source:
               Grant Number:       Anticipated Grant Submission Date:
UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office         Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                                  Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                               Fax: (402) 559-4970
  New Project Submission Form - Open at Children's ONLY (Version 02/10/2010)                                            Page 50 of 74
    B. MULTI-CENTER INSTITUTIONAL TRIAL: Protocol in which a local PI is participating in a study that is
       designed and developed at another institution and where more than one IRB approval is required.

    C. NATIONAL COOPERATIVE GROUP TRIAL: Protocol that is initiated by an NCI funded study group and
       receives CTEP review. NOTE: Only those study groups listed below qualify for this classification.
           ACRIN            CALGB         ECOG                  GOG              NSABP                RTOG
           ACSOG            COG           EORTC                 NCICA            NCCTG                SWOG
         Did you as investigator play a major role in the development of this protocol?                No         Yes
         If yes, please explain your level of participation.

    D. INDUSTRIAL TRIAL: Protocol that is designed, developed and monitored by Industry.
         Did you as investigator play a major role in the development of this protocol?                No         Yes
         If YES, please explain your level of participation.

    E. OTHER EXTERNALLY PEER-REVIEWED TRIAL: R01, P01 or other trial funded by NIH or supported by other
       peer-reviewed funding organizations, such as the ACS, the Komen Foundation, Leukemia and lymphoma
       Society, U.S. Army (DOD) etc.
         Did you as investigator play a major role in the development of this protocol?                No         Yes
         If YES, please explain your level of participation.

SECTION IV: NCI CLASSIFICATION and PHASE (for intervention trials) or TYPE (for non-intervention trials)

    A. THERAPEUTIC INTERVENTION TRIAL: Clinical trial with therapeutic intent using an agent or device (e.g.
       drugs, radiation, surgery, and/or biological agents).

    B. PREVENTION INTERVENTION TRIAL: Clinical trial for the modulation of cancer risk and inhibition of cancer
       progression using behavioral modification, nutrition, dietary or chemoprevention interventions.

         1. PHASE: For either (A) Therapeutic or (B) Prevention Intervention Trials, please indicate the study PHASE.
               Pilot or Feasibility: Protocols where primary objective is to collect preliminary data to plan a future
               protocol. The trial must be limited in duration and the investigator must specify future plans.
               Phase I: Protocols designed to determine a safe method/dose for Phase II trials and define acute
               effects that occur with a relatively high frequency in normal tissues.
               Phase II: Protocols designed to a) determine whether a treatment/agent has anti-tumor activity and
               b) estimate the response rate in a defined patient population.
               Phase III: Protocols designed to compare the new drug or treatment modality with standard
               treatment or observation, if no standard treatment exists.
               Phase IV: Protocols designed to evaluate side effects that were not apparent in Phase III trials after
               a treatment has been approved and is being marketed.
               Combination:        Phase I/II         Other: Please specify



UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office   Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                            Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                         Fax: (402) 559-4970
  New Project Submission Form - Open at Children's ONLY (Version 02/10/2010)                                      Page 51 of 74
    C. NON-INTERVENTION TRIAL: 1) Epidemiologic, outcome, or other observational study; or 2) study
       associated with a clinical trial or other biological study using clinical specimens that can be linked to individual
       patient or participant data.

         1. TYPE: For Non-Intervention Trials, please indicate the study TYPE.
               Screening, Early Detection, or Diagnostic Trial: Protocol designed to test the efficacy of devices,
               techniques, procedures, or tests for earlier/more accurate detection or diagnosis of disease.
                   Supportive Care Trial: Protocol designed to improve the comfort and quality of life for the patient.
                   Epidemiologic/Observational Trial: Study among cancer patients and healthy populations that
                   involve no intervention or alteration in the status of the participants (e.g., surveillance, risk
                   assessment, environmental and behavioral studies, etc.)
                   Ancillary or Companion Trial: Auxiliary study that is stimulated by, but not a required part of, a
                   main clinical trail, and that utilizes patient or other resources of the main trial to generate information
                   relevant to it.
                   NOTE: Companion or ancillary studies must be linked to an active trial, or epidemiologic or other
                   observational study (screening, early detection, diagnostic; therapeutic; or prevention) and should
                   include only patients accrued to that trial or study.
                   Correlative Trial: Laboratory based study using specimens to assess cancer risk, clinical outcomes,
                   response to therapies, etc.
                   NOTE: Correlative studies must be linkable to other patient data.

SECTION V: Please indicate 1) whether this protocol is a transplant protocol; 2) if it involves randomized
treatment or an investigational drug; and 3) if it is intended for newly diagnosed or relapsed subjects, or both.

Transplant Protocol:                  Yes          No
Randomized Treatment:                 Yes          No
Investigational Drug:                 Yes          No
Intended Subjects:                    Newly Diagnosed                 Relapsed     Both Newly Diagnosed and Relapsed


SECTION VI: Please identify the tumor type/s and/or anatomic site/s the protocol addresses.

    Ancillary                                            Genitourinary                                Multiple Myeloma
    Brain and Neuro                                      GVHD                                         MDS
    Breast                                               GYN - Other                                  Ovarian
    Cervical                                             Head/Neck                                    Pancreatic
    Colorectal                                           Hepatocellular                               Prostate
    Endocrine                                            Leukemia                                     Sarcoma
    Endometrial                                          Lung                                         Other
    Esophageal                                           Lymphoma                                     Please Specify:
    GI - Other                                           Melanoma/Skin



UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office    Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                             Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                          Fax: (402) 559-4970
  New Project Submission Form - Open at Children's ONLY (Version 02/10/2010)                                       Page 52 of 74
   SECTION VII: Does this protocol compete with other ongoing studies currently open to accrual at
   Children's?

        Yes        No

   If YES, please list any competing protocols (i.e. those with similar eligibility criteria) and rank them in the order of
   priority that they would be offered to the patient (i.e. #1, #2).
   NOTE: Per NCI Guidelines, protocols must be ranked in the following order of priority: 1) Investigator-Initiated
   Institutional trials; 2) Multi-Center Institutional trials; 3) National Cooperative Group trials; 4) Industry trials; and 5)
   Other Externally Peer Reviewed trials. A list of active Children's protocols is available from the Eppley Cancer
   Center PRMS office or on their web site at http://www.unmc.edu/ccto/.
   Rank       IRB #        Protocol Classification                                              Title
                          (Investigator-Initiated, Multi-
                         Center, National Cooperative
                           Group, Industrial or Other
                          Externally Peer Reviewed)




SECTION VIII: ACCRUAL PROJECTION, INFORMATION and REPORTING:

   C. During the NEXT 12 MONTHS:
   1. What is the targeted accrual for the entire study, including all participating sites?
   2. What is the targeted accrual at Children's?

   D. During the DURATION OF THE STUDY:
   1. What is the targeted accrual for the entire study, including all participating sites?
   2. What is the targeted accrual at Children's?
   3. What is the targeted number of years this study will remain active?

   C. ACCRUAL REPORTING REQUIREMENTS:

          I agree to submit copies of the consent forms for each subject registered to this protocol to the UNMC Eppley
          Cancer Center PRMS Office (Campus Zip 6805) within one week of enrollment.




   UNMC Eppley Cancer Center Clinical Trials Office                               Eppley Science Hall (ESH) Room 10006 and 10007
   986805 Nebraska Medical Center                                                                           Phone: (402) 559-4969
   Omaha NE 68198-6805                                                                                        Fax: (402) 559-4970
     New Project Submission Form - Open at Children's ONLY (Version 02/10/2010)                                     Page 53 of 74
SECTION IX: New Protocol Submission Checklist (please mark all that apply and submit in order listed)
        Original Signed and Dated SRC New Protocol Submission Form - required
        Cover letter and/or copy of relevant correspondence (if applicable)
        Copy of the IRB Application for Biomedical Research form, Sections I and II - required
        Consent form/s (if applicable)
        Data collection form/s (if applicable) - required for all Investigator-Initiated trials
        Investigator Brochure (if applicable)
        Grant application (if applicable)
        Protocol with version and date clearly marked on the face page


        NOTE: A protocol in SRC format is required for all Investigator-Initiated and Therapeutic Intervention Pilot trials.
        Instructions on preparing a protocol in SRC format are available from the UNMC Eppley Cancer Center Clinical
        Trials office or on their web site at http://www.unmc.edu/ccto/.


    ___________________________________                                            ________________
        Signature of Principal Investigator                                               Date




    UNMC Eppley Cancer Center Clinical Trials Office                                     Eppley Science Hall (ESH) Room 10006 and 10007
    986805 Nebraska Medical Center                                                                                 Phone: (402) 559-4969
    Omaha NE 68198-6805                                                                                              Fax: (402) 559-4970
      New Project Submission Form - Open at Children's ONLY (Version 02/10/2010)                                           Page 54 of 74
                     APPENDIX E.1: CONTINUING REVIEW SUBMISSION FORM
                           For A) Investigator-Initiated Institutional; B) Multi-Center Institutional;
                             C) Industrial; or D) Other Externally Peer Reviewed Protocols Only

Instructions: Please complete and submit this form to the UNMC Eppley Cancer Center Protocol Review and
Monitoring System (PRMS) Office (Campus Zip 6805) by the fourth Friday of each month. Submissions received
after this deadline will be reviewed at the subsequent SRC meeting. NOTE: In 2010, the submission deadline is the
3rd Friday in February (02/19/10), and the 4th Wednesday in November and December (11/24/10 and 12/22/10).

SECTION I: BASIC PROTOCOL DATA
Current IRB#:
Title:
PI:                                                       Phone:                              Email:
Study Coordinator/Contact:                                Phone:                              Email:


SECTION II: CONTINUING REVIEW WITH CHANGE                                   Yes        No      If YES, please see Section VI

SECTION III: PROTOCOL STATUS

Date of initial IRB approval:
      Actively Accruing Patients
      Study on Hold           Date study placed on hold
      Note: If study was previously on hold and is no longer on hold, please give date study was taken off hold
      Closed to Accrual    Date study was closed to accrual
      Reason study was closed to accrual

SECTION IV: ACCRUAL
A. What was the ORIGINAL target accrual goal at UNMC/The Nebraska Medical Center, per year and per
   duration of the study (Example: 25 subjects per year for 5 years)?
B. What is the CURRENT target accrual goal at UNMC/The Nebraska Medical Center, per year and per
   duration of the study (Example: 25 subjects per year for 5 years)?
C. How many total subjects have been accrued over what period of time at UNMC/The Nebraska Medical
   Center (Example: 15 subjects since 01/01/00)?
D. How many subjects have been accrued at UNMC/The Nebraska Medical Center since the last SRC review?

E. What percentage of the CURRENT target accrual goal has been reached to date at UNMC/The Nebraska
   Medical Center?
      If the accrual to date is less than 30%, what plans do you have to improve it? (Please be specific.)
UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office               Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                                        Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                                     Fax: (402) 559-4970
  Continuing Review Submission Form for Institutional, Industry and Other Peer Reviewed Studies (Version 02/10/2010)          Page 55 of 74
     NOTE: The SRC may vote to close a protocol if the accrual to date is less than 30% of the projected accrual
     at UNMC/The Nebraska Medical Center and if there is reason to believe that the protocol will not be able to
     meet its original or current accrual projection.
F. If this is an Investigator Initiated Institutional Multi-Site trial or a Multi-Center Institutional trial:
     What is the CURRENT target accrual goal at all participating sites, per year and per duration of the study
     (Example: 25 subjects per year for 5 years)?
     What percentage of the total accrual goal has been reached TO DATE at all participating sites?
G. What date was the first subject consented?
H. Did subject recruitment begin as soon as the study received approval by the IRB?                                    Yes     No
     If NO, please explain the reason for the recruitment delay.


SECTION V: REQUEST FOR CHANGES TO THE PROTOCOL

A. Does this Continuing Review include a Request for Change?                                Yes        No
     If changes in personnel (other than change of Principal Investigator) are the only changes to this protocol,
     complete section “B” below and Do Not submit an SRC Change form with this Continuing Review.
     For all other changes (Example: All Major Changes, Addition or Deletion of Study Site/s, Reporting
     Requirements, Title Changes and Other Minor Changes), please complete an SRC Request for Change
     form and submit along with this Continuing Review.

B. Personnel Change/s: (Note: Change of PI must be accompanied by a Request for Change form)
     1. Not Applicable:
     2. Personnel to be added:
     3. Personnel to be deleted:

SECTION VI: PREVIOUSLY SUBMITTED or APPROVED CHANGES TO THE PROTOCOL

A. Since the last SRC Continuing Review, have any major developments occurred in the scientific area that
   affect the specific objectives of this study? Yes    No
B. Since the last SRC Continuing Review, have any major changes been made to the protocol? (Example: drug
   dosage changes, modifications to the treatment plan, amendments from the sponsor, changes resulting from
   adverse event, etc.)    Yes     No
     If YES to either A or B above:
     1. Has the protocol been revised accordingly?                       Yes        No
     2. Please list protocol revisions and provide SRC approval dates.

UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office               Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                                        Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                                     Fax: (402) 559-4970
  Continuing Review Submission Form for Institutional, Industry and Other Peer Reviewed Studies (Version 02/10/2010)          Page 56 of 74
C. Since the last SRC Continuing Review, have any changes been made to the Investigator Brochure?
          Yes       No
     If YES to C above:
     1. Has the protocol been revised as a result of these changes?                            Yes        No
     2. Has the revised Investigator Brochure been submitted to the SRC?                               Yes        No

SECTION VII: Does this protocol compete with other ongoing studies?                                       Yes          No

If YES, please list any competing protocols (i.e. those with similar eligibility criteria) and rank them in the order of
priority that they would be offered to the patient (i.e. #1, #2).
NOTE: Per NCI Guidelines, protocols must be ranked in the following order of priority: 1) Investigator-Initiated
Institutional trials; 2) Multi-Center Institutional trials; 3) National Cooperative Group trials; 4) Industry trials; and 5)
Other Externally Peer Reviewed trials. A list of active protocols is available from the UNMC Eppley Cancer Center
PRMS office or on their web site at http://www.unmc.edu/ccto/.
Rank IRB #             Protocol Classification                                                        Title
                      (Investigator-Initiated, Multi-
                     Center, National Cooperative
                       Group, Industrial or Other
                      Externally Peer Reviewed)




SECTION VIII: Continuing Review Submission Checklist (please mark all that apply and submit in order
              listed)
     Original Signed and Dated SRC Continuing Review Submission Form - required
     Cover letter and/or copy of relevant correspondence (if applicable)
     Copy of the IRB Application for Continuing Review form (Section I and II) - required
     The REVISED protocol with version and date clearly marked on the face page (if applicable)




___________________________________                                                                ______________________
    Signature of Principal Investigator                                                                     Date




UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office               Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                                        Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                                     Fax: (402) 559-4970
  Continuing Review Submission Form for Institutional, Industry and Other Peer Reviewed Studies (Version 02/10/2010)          Page 57 of 74
                     APPENDIX E.2: CONTINUING REVIEW SUBMISSION FORM
                                        For National Cooperative Group Protocols Only

Instructions: Please complete and submit this form to the UNMC Eppley Cancer Center Protocol Review and
Monitoring System (PRMS) Office (Campus Zip 6805) by the fourth Friday of each month. Submissions received
after this deadline will be reviewed at the subsequent SRC meeting. NOTE: In 2010, the submission deadline is the
3rd Friday in February (02/19/10), and the 4th Wednesday in November and December (11/24/10 and 12/22/10).

SECTION I: BASIC PROTOCOL DATA
Current IRB#:
Title:
PI:                                                       Phone:                   Email:
Study Coordinator/Contact:                                Phone:                   Email:


SECTION II: PROTOCOL STATUS
Date of initial IRB approval:
      Actively Accruing Patients
      Study on Hold           Date study place on hold
      Note: If study was previously on hold and is no longer on hold, please give date study was taken off hold
      Closed to Accrual    Date study was closed to accrual
      Reason study was closed to accrual


SECTION III: ACCRUAL
A. What was the ORIGINAL target accrual goal at UNMC/The Nebraska Medical Center, per year and per
   duration of the study (Example: 25 subjects per year for 5 years)?
B. What is the CURRENT target accrual goal at UNMC/The Nebraska Medical Center, per year and per
   duration of the study (Example: 25 subjects per year for 5 years)?
C. How many total subjects have been accrued and over what period of time at UNMC/The Nebraska Medical
   Center (Example: 15 subjects since 01/01/00)?
D. How many subjects have been accrued at UNMC/The Nebraska Medical Center since the last SRC review?

E. What percentage of the CURRENT target accrual goal has been reached to date at UNMC/The Nebraska
   Medical Center?
      If the accrual to date is less than 30%, what plans do you have to improve it? (Please be specific.)
      NOTE: The SRC may vote to close a protocol if the accrual to date is less than 30% of the projected accrual
      at UNMC/The Nebraska Medical Center and if there is reason to believe that the protocol will not be able to
      meet its original or current accrual projection.
UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office     Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                              Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                           Fax: (402) 559-4970
  Continuing Review Form for National Cooperative Group Trials Only (02/10/2010                                     Page 58 of 74
F. What is the CURRENT target accrual goal at all participating sites, per year and per duration of the study
   (Example: 25 subjects per year for 5 years)?
G. What percentage of the total accrual goal has been reached to date at all participating sites?
H. What date was the first subject consented?
I.     Did subject recruitment begin as soon as the study received approval by the IRB?                        Yes      No
       If NO, please explain the reason for the recruitment delay.


SECTION IV: CHANGES TO THE PROTOCOL SINCE THE LAST CONTINUING REVIEW
Have any of the following changes been made to the protocol since the last continuing review?                            Yes       No
If YES, please summarize these changes below.
       A. Major Change(s):
            1. Addition or reduction of subject accrual goals:
            2. Change(s) to eligibility criteria:
            3. Change(s) of Principal Investigator (PI):
       B. Minor Change(s):
            1. Personnel Change(s) - Other than Change in PI
                a. Personnel added:
                b. Personnel deleted:
            2. Addition or deletion of Study Site(s)
                a. Study Site(s) added:
                b. Study Site(s) deleted:
            3. Title change – Please list new title:

SECTION V: Does this protocol compete with other ongoing studies?                               Yes       No

If YES, please list any competing protocols (i.e. those with similar eligibility criteria) and rank them in the order of
priority that they would be offered to the patient (i.e. #1, #2).
NOTE: Per NCI Guidelines, protocols must be ranked in the following order of priority: 1) Investigator-Initiated
Institutional trials; 2) Multi-Center Institutional trials; 3) National Cooperative Group trials; 4) Industry trials; and 5)
Other Externally Peer Reviewed trials. A list of active protocols is available from the UNMC Eppley Cancer Center
PRMS office or on their web site at http://www.unmc.edu/ccto/.




UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office        Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                                 Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                              Fax: (402) 559-4970
     Continuing Review Form for National Cooperative Group Trials Only (02/10/2010                                     Page 59 of 74
Rank IRB #             Protocol Classification                                             Title
                      (Investigator-Initiated, Multi-
                     Center, National Cooperative
                       Group, Industrial or Other
                      Externally Peer Reviewed)




SECTION VI: Continuing Review Submission Checklist (please mark all that apply and submit in order
listed)
           Original Signed and Dated SRC Continuing Review Submission Form - required
           Cover letter and/or copy of relevant correspondence (if applicable)
           Copy of the IRB Application for Continuing Review form (Section I and II) - required
           The REVISED protocol with version and date clearly marked on the face page (if applicable)

    NOTE: Investigator-Initiated and Therapeutic Intervention Pilot protocols must be in SRC format. Instructions on
    preparing a protocol in SRC format are available from the UNMC Eppley Cancer Center PRMS office or on their
    web site at http://www.unmc.edu/ccto/.


___________________________________                                                     ______________________
    Signature of Principal Investigator                                                          Date




UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office     Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                              Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                           Fax: (402) 559-4970
  Continuing Review Form for National Cooperative Group Trials Only (02/10/2010                                     Page 60 of 74
                     APPENDIX E.3: CONTINUING REVIEW SUBMISSION FORM
                                      For National Cooperative Group Protocols
                             Open ONLY at Children's Hospital and Medical Center (Children's)

Instructions: Please complete and submit this form to the UNMC Eppley Cancer Center Protocol Review and
Monitoring System (PRMS) Office (Campus Zip 6805) by the fourth Friday of each month. Submissions received
after this deadline will be reviewed at the subsequent SRC meeting. NOTE: In 2010, the submission deadline is the
3rd Friday in February (02/19/10), and the 4th Wednesday in November and December (11/24/10 and 12/22/10).

SECTION I: BASIC PROTOCOL DATA
Current IRB#:                                             Previous Children's IRB #:
Title:
PI:                                                       Phone:                             Email:
Study Coordinator/Contact:                                Phone:                             Email:


SECTION II: PROTOCOL STATUS
Date of initial IRB approval:                             Date of initial Children's IRB approval:
      Actively Accruing Patients
      Study on Hold           Date study place on hold
      Note: If study was previously on hold and is no longer on hold, please give date study was taken off hold
      Closed to Accrual    Date study was closed to accrual
      Reason study was closed to accrual


SECTION III: ACCRUAL
A. What was the ORIGINAL target accrual goal at Children's, per year and per duration of the study (Example:
   25 subjects per year for 5 years)?
B. What is the CURRENT target accrual goal at Children's, per year and per duration of the study (Example: 25
   subjects per year for 5 years)?
C. How many total subjects have been accrued and over what period of time at Children's (Example: 15
   subjects since 01/01/00)?
D. How many subjects have been accrued at Children's since the last SRC review?
E. What percentage of the CURRENT target accrual goal has been reached to date at Children's?
      If the accrual to date is less than 30%, what plans do you have to improve it? (Please be specific.)
      NOTE: The SRC may vote to close a protocol if the accrual to date is less than 30% of the projected accrual
      at Children's and if there is reason to believe that the protocol will not be able to meet its original or current
      accrual projection.

UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office              Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                                       Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                                    Fax: (402) 559-4970
  Continuing Review Form for National Cooperative Group Trials - Open at Children's ONLY (02/10/2010)                        Page 61 of 74
F. What is the CURRENT target accrual goal at all participating sites, per year and per duration of the study
   (Example: 25 subjects per year for 5 years)?
G. What percentage of the total accrual goal has been reached to date at all participating sites?
H. What date was the first subject consented?
I.     Did subject recruitment begin as soon as the study received approval by the IRB?                                Yes       No
       If NO, please explain the reason for the recruitment delay.

SECTION IV: CHANGES TO THE PROTOCOL SINCE THE LAST CONTINUING REVIEW
Have any of the following changes been made to the protocol since the last continuing review?                                     Yes       No
If YES, please summarize these changes below.
       A. Major Change(s):
            1. Addition or reduction of subject accrual goals:
            2. Change(s) to eligibility criteria:
            3. Change(s) of Principal Investigator (PI):
       B. Minor Change(s):
            4. Personnel Change(s) - Other than Change in PI
                a. Personnel added:
                b. Personnel deleted:
            5. Addition or deletion of Study Site(s)
                a. Study Site(s) added:
                b. Study Site(s) deleted:
            6. Title change – Please list new title:

SECTION V: Does this protocol compete with other ongoing studies currently open to accrual at
Children's?
             Yes      No

If YES, please list any competing protocols (i.e. those with similar eligibility criteria) and rank them in the order of
priority that they would be offered to the patient (i.e. #1, #2).
NOTE: Per NCI Guidelines, protocols must be ranked in the following order of priority: 1) Investigator-Initiated
Institutional trials; 2) Multi-Center Institutional trials; 3) National Cooperative Group trials; ; 4) Industry trials; and 5)
Other Externally Peer Reviewed trials. A list of active Children's protocols is available from the UNMC Eppley
Cancer Center PRMS office or on their web site at http://www.unmc.edu/ccto/.




UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office                 Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                                          Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                                       Fax: (402) 559-4970
     Continuing Review Form for National Cooperative Group Trials - Open at Children's ONLY (02/10/2010)                        Page 62 of 74
Rank IRB #             Protocol Classification                                                          Title
                      (Investigator-Initiated, Multi-
                     Center, National Cooperative
                       Group, Industrial or Other
                      Externally Peer Reviewed)




SECTION VI: Continuing Review Submission Checklist (please mark all that apply and submit in order
listed)

           Original Signed and Dated SRC Continuing Review Submission Form - required
           Cover letter and/or copy of relevant correspondence (if applicable)
           Copy of the IRB Application for Continuing Review form (Section I and II) - required
           The REVISED protocol with version and date clearly marked on the face page (if applicable)

    NOTE: Investigator-Initiated and Therapeutic Intervention Pilot protocols must be in SRC format. Instructions on
    preparing a protocol in SRC format are available from the UNMC Eppley Cancer Center PRMS office or on their
    web site at http://www.unmc.edu/ccto/.


___________________________________                                                               ______________________
    Signature of Principal Investigator                                                                    Date




UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office              Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                                       Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                                    Fax: (402) 559-4970
  Continuing Review Form for National Cooperative Group Trials - Open at Children's ONLY (02/10/2010)                        Page 63 of 74
                   APPENDIX F.1: REQUEST FOR CHANGE SUBMISSION FORM
                          For A) Investigator-Initiated Institutional; B) Multi-Center Institutional;
                            C) Industrial; or D) Other Externally Peer Reviewed Protocols Only

               NOTE: Changes to National Cooperative Group trials do not require SRC review or approval.
Instructions: Please complete and submit this form to the UNMC Eppley Cancer Center Protocol Review and
Monitoring System (PRMS) Office (Campus Zip 6805) by the fourth Friday of each month. Submissions received
after this deadline will be reviewed at the subsequent SRC meeting. NOTE: In 2010, the submission deadline is the
3rd Friday in February (02/19/10), and the 4th Wednesday in November and December (11/24/10 and 12/22/10).

SECTION I: BASIC PROTOCOL DATA


Current IRB#:
Title:
PI:                                                                Phone:                Email:
Study Coordinator/Contact:                                         Phone:                Email:


SECTION II: PROTOCOL STATUS
      Actively Accruing Patients
      Study on Hold                     Date study placed on hold
      Note: If study was previously on hold and is no longer on hold, please give date study was taken off hold
      Closed to Accrual             Date study was closed to accrual
      Reason study was closed to accrual

SECTION III: CHANGES THAT ARE BEING REQUESTED

                        Major Change/s                                                            Minor Change/s
      Addition or reduction of subject accrual goals                            Personnel change/s (Other than Change in PI)
                                                                                Personnel to be added:
      Change/s to design, method, or procedures
                                                                                Personnel to be deleted:
      Change/s to drug dosage or delivery
                                                                                Addition or deletion of Study Site/s
      Change/s to eligibility criteria                                          Study Site/s to be added:
      Change/s to data collection forms                                         Study Site/s to be deleted:

      Change/s to the Investigator Brochure that affect the                     Reporting requirements
      protocol**                                                                Title change – Please list new title:
      Change of Principal Investigator (PI)                                     Other – Please explain:
      Other: Please explain:
** While the SRC is required to have the most current copy of the Investigator Brochure (IB) on file, if changes to
   the IB do not cause a change to the protocol, no "Request for Change" needs to be submitted.
UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office          Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                                   Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                                Fax: (402) 559-4970
  Request for Change Submission Form (Version 02/10/2010)                                                                Page 64 of 74
B. Are the proposed changes the result of an adverse event?                     Yes     No
     If YES, please attach a copy of the adverse event report.

C. Are the proposed changes the result of a request for funding/grant application?                    Yes      No
     If the proposed change (including title change) is the result of a new request for financial support, please
     attach a copy of the schema and abstract from the grant.

D. Are the proposed changes the result of a protocol amendment?                       Yes       No
     If YES, provide version number and date

SECTION IV: JUSTIFICATION FOR REQUESTED CHANGES

For all changes to the protocol, all changes to the data collection forms and/or changes in the investigator brochure
that affect the protocol, please describe the justification for each of the requested changes.

Change requested: Summarize the                    Change from: Summarize what                 Rationale for Change: Give the
change or include the proposed                     is being replaced.                          scientific rationale for the change
language.                                                                                      or preliminary findings that
                                                                                               indicate the need for change.




SECTION V: IMPACT OF THE REQUESTED CHANGES

A. If this is an Investigator-Initiated Institutional protocol and accrual has been changed, has a biostatistician been
   consulted to ensure that the statistical considerations are appropriate?        Yes    No      N/A

B. If the requested changes involve eligibility or accrual, do changes cause the protocol to compete with other
   ongoing studies?      Yes     No
    If YES, please list any competing protocols (i.e. those with similar eligibility criteria) and rank them in the order of
    priority that they would be offered to the patient (i.e. #1, #2).
UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office     Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                              Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                           Fax: (402) 559-4970
  Request for Change Submission Form (Version 02/10/2010)                                                           Page 65 of 74
    NOTE: Per NCI Guidelines, protocols must be ranked in the following order of priority: 1) Investigator-Initiated
    Institutional trials; 2) Multi-Center Institutional trials; 3) National Cooperative Group trials; ; 4) Industry trials;
    and 5) Other Externally Peer Reviewed trials. A list of active protocols is available from the UNMC Eppley
    Cancer Center PRMS office or on their web site at http://www.unmc.edu/ccto/.

Rank       IRB#         Protocol Classification                                            Title
                        (Investigator-Initiated, Multi-
                       Center, National Cooperative
                         Group, Industrial or Other
                        Externally Peer Reviewed)




SECTION VI: Request for Change Checklist (please mark all that apply and submit in order listed)
         Original Signed and Dated SRC Request for Change Submission Form - required
         Cover letter and/or copies of any correspondence related to this change (if applicable)
         Copy of the IRB Request for Change – Section I and II - required, if submitted to the IRB
         The REVISED Data collection form/s (if applicable)
         The REVISED Investigator Brochure (if applicable)
         Copy of the schema and abstract from the grant (If the proposed change, including title change, is the result
    of a new
         request for financial support)
         The REVISED protocol with version and date clearly marked on the face page (if applicable)

    NOTE: Investigator-Initiated and Therapeutic Intervention Pilot protocols must be in SRC format. Instructions on
    preparing a protocol in SRC format are available from the UNMC Eppley Cancer Center PRMS office or on their
    web site at http://www.unmc.edu/ccto/.


___________________________________                                                   ______________________
    Signature of Principal Investigator                                                        Date




UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office   Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                            Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                         Fax: (402) 559-4970
  Request for Change Submission Form (Version 02/10/2010)                                                         Page 66 of 74
                   APPENDIX F.2: REQUEST FOR CHANGE SUBMISSION FORM
                          For A) Investigator-Initiated Institutional; B) Multi-Center Institutional;
                               C) Industrial; or D) Other Externally Peer Reviewed Protocols
                          Open ONLY at Children's Hospital and Medical Center (Children's)
               NOTE: Changes to National Cooperative Group trials do not require SRC review or approval.
Instructions: Please complete and submit this form to the UNMC Eppley Cancer Center Protocol Review and
Monitoring System (PRMS) Office (Campus Zip 6805) by the fourth Friday of each month. Submissions received
after this deadline will be reviewed at the subsequent SRC meeting. NOTE: In 2010, the submission deadline is the
3rd Friday in February (02/19/10), and the 4th Wednesday in November and December (11/24/10 and 12/22/10).

SECTION I: BASIC PROTOCOL DATA
Current IRB#:                                                      Previous Children's IRB#:
Title:
PI:                                                                Phone:                Email:
Study Coordinator/Contact:                                         Phone:                Email:


SECTION II: PROTOCOL STATUS
      Actively Accruing Patients
      Study on Hold                     Date study placed on hold
      Note: If study was previously on hold and is no longer on hold, please give date study was taken off hold
      Closed to Accrual             Date study was closed to accrual
      Reason study was closed to accrual

SECTION III: CHANGES THAT ARE BEING REQUESTED

                        Major Change/s                                                            Minor Change/s
      Addition or reduction of subject accrual goals                            Personnel change/s (Other than Change in PI)
                                                                                Personnel to be added:
      Change/s to design, method, or procedures
                                                                                Personnel to be deleted:
      Change/s to drug dosage or delivery
                                                                                Addition or deletion of Study Site/s
      Change/s to eligibility criteria                                          Study Site/s to be added:
      Change/s to data collection forms                                         Study Site/s to be deleted:

      Change/s to the Investigator Brochure that affect the                     Reporting requirements
      protocol**                                                                Title change – Please list new title:
      Change of Principal Investigator (PI)                                     Other – Please explain:
      Other: Please explain:
** While the SRC is required to have the most current copy of the Investigator Brochure (IB) on file, if changes to
   the IB do not cause a change to the protocol, no "Request for Change" needs to be submitted.

UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office          Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                                   Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                                Fax: (402) 559-4970
  Request for Change Submission Form - Open at Children's ONLY (Version 02/10/2010)                                      Page 67 of 74
B. Are the proposed changes the result of an adverse event?                           Yes     No
     If YES, please attach a copy of the adverse event report.

C. Are the proposed changes the result of a request for funding/grant application?                          Yes      No
     If the proposed change (including title change) is the result of a new request for financial support, please
     attach a copy of the schema and abstract from the grant.

D. Are the proposed changes the result of a protocol amendment?                             Yes       No
     If YES, provide version number and date

SECTION IV: JUSTIFICATION FOR REQUESTED CHANGES

For all changes to the protocol, all changes to the data collection forms and/or changes in the investigator brochure
that affect the protocol, please describe the justification for each of the requested changes.

Change requested: Summarize the                    Change from: Summarize what                       Rationale for Change: Give the
change or include the proposed                     is being replaced.                                scientific rationale for the change
language.                                                                                            or preliminary findings that
                                                                                                     indicate the need for change.




SECTION V: IMPACT OF THE REQUESTED CHANGES

A. If this is an Investigator-Initiated Institutional protocol and accrual has been changed, has a biostatistician been
   consulted to ensure that the statistical considerations are appropriate?        Yes    No      N/A

B. If the requested changes involve eligibility or accrual, do changes cause the protocol to compete with other
   ongoing studies?      Yes     No
    If YES, please list any competing protocols (i.e. those with similar eligibility criteria) and rank them in the order of
    priority that they would be offered to the patient (i.e. #1, #2).
UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office           Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                                    Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                                 Fax: (402) 559-4970
  Request for Change Submission Form - Open at Children's ONLY (Version 02/10/2010)                                       Page 68 of 74
NOTE: Per NCI Guidelines, protocols must be ranked in the following order of priority: 1) Investigator-Initiated
Institutional trials; 2) Multi-Center Institutional trials; 3) National Cooperative Group trials; ; 4) Industry trials; and 5)
Other Externally Peer Reviewed trials. A list of active Children's protocols is available from the UNMC Eppley
Cancer Center PRMS office or on their web site at http://www.unmc.edu/ccto/.
Rank       IRB#         Protocol Classification                                                  Title
                       (Investigator-Initiated, Multi-
                      Center, National Cooperative
                        Group, Industrial or Other
                       Externally Peer Reviewed)




SECTION VI: Request for Change Checklist (please mark all that apply and submit in order listed)
     Original Signed and Dated SRC Request for Change Submission Form - required
     Cover letter and/or copies of any correspondence related to this change (if applicable)
     Copy of the IRB Request for Change – Section I and II required, if submitted to the IRB
     The REVISED Data collection form/s (if applicable)
     The REVISED Investigator Brochure (if applicable)
     Copy of the schema and abstract from the grant (If the proposed change, including title change, is the result of a
     new request for financial support)
     The REVISED protocol with version and date clearly marked on the face page (if applicable)

    NOTE: Investigator-Initiated and Therapeutic Intervention Pilot protocols must be in SRC format. Instructions on
    preparing a protocol in SRC format are available from the UNMC Eppley Cancer Center PRMS office or on their
    web site at http://www.unmc.edu/ccto/.


___________________________________                                                         ______________________
    Signature of Principal Investigator                                                              Date




UNMC Eppley Cancer Center Protocol Review and Monitoring System (PRMS) Office         Eppley Science Hall (ESH) Room 10006 and 10007
986805 Nebraska Medical Center                                                                                  Phone: (402) 559-4969
Omaha NE 68198-6805                                                                                               Fax: (402) 559-4970
  Request for Change Submission Form - Open at Children's ONLY (Version 02/10/2010)                                     Page 69 of 74

				
DOCUMENT INFO