Pediatric Oncology Subcommittee of ODAC Report of Meeting by tsw71223


									  Pediatric Oncology
Subcommittee of ODAC
     Report of Meeting
     October 20, 2005

  Pamela J. Haylock, RN, MA
       Consumer Representative

        presenting on behalf of

   Gregory H. Reaman, MD
     Subcommittee Chair

   Subcommittees are advisory to the
    “parent” committee
       do not directly advise FDA
   Parent committee reviews
    subcommittee recommendations;
    advises FDA
   At least 2 members of parent
    committee serve on the subcommittee
   No charter or official roster
Pediatric Subcommittee to ODAC
BPCA– Sec 15
   Evaluate and to the extent practicable,
    prioritize new and emerging therapeutic
    alternatives to treat pediatric cancer
   Provide recommendations and guidance
    to ensure that children with cancer
    have timely access to the most
    promising new cancer therapeutics
   Advise on ways to improve consistency
    in the availability of new therapeutic
Pediatric Subcommittee
Members & Consultants for the
October 20, 2005 Meeting
From ODAC:
 Gregory H. Reaman, MD, Chairperson
    Pediatric Oncology & Chair, COG
    Prof Pediatrics, GWU, School of Medicine
    Washington, D.C.
   Pamela Haylock, RN, MA
    Consumer Representative to ODAC
    Oncology Consultant & Doctoral Student
    UTMB Graduate School of Biomedical Sciences
    Galveston, TX
   Jeffrey Barrett, PhD              Michael Link, MD
    Assoc. Prof, Pediatrics,           Stanford, School of Medicine
    Children’s Hospital of             Division of Hematology
    Philadelphia                       Stanford, CA
   James Boyett, PhD                 Charles Reynolds, MD
    Dept. Biostatistics                Children’s Hosp of LA/USC
    St. Jude Children’s Research       Los Angeles, CA
    Hospital, Memphis, TN             Victor Santana, MD
   Jerry Finklestein, MD              Dept Hematology Oncology
    Jonathan Jacques Children’s        St. Jude, Children’s Research
    CA Center                          Hospital, Memphis, TN
    Long Beach, CA
   Cindy Schwartz, MD                Thomas Walsh, MD
    Rhode Island Hospital              Chief, Immunocompromised
                                       Host Section, NCI
    Dept. Pediatrics - Hem/Onc
                                      Naomi Winick, MD
    Providence, RI
                                       Dept. Pediatrics – Hem/Onc
   Malcolm Smith, MD, PhD
                                       UT, Southwestern Med Ctr
    Head, Ped Section, CIB
                                       Dallas, TX
   Clinton Stewart, PhD
    St. Jude Children’s Research
    Memphis, TN
   Marilyn S. Eichner – Rockville, MD
    Patient Representative
   Cathy A. O’Connell – Belchertown, MA
    Patient Representative
   Eugene Sun, M.D.
    Industry Representative
    Global Pharmaceutical Development
    Abbott Laboratories, Abbot Park, IL
     FDA Participants
   Richard Pazdur, MD
    Director, Office of Oncology Products
   Karen Weiss, MD
    Deputy Director, Office of Oncology Products
   Patricia Keegan, MD
    Director, Div of Biologic Oncology Products
   Robert Justice, MD
    Acting Director, Division of Oncology Drug Products
   Ramzi Dagher, MD
    Medical Team Leader, Division Oncology Drug Products
    FDA Participants
   Joseph Gootenberg, MD
    Medical Team Leader, Divsion of Pediatric Drug Development
   Lisa Mathis, MD
    Acting Director, Division of Pediatric Drug Development
    Office of Counterterrorism & Pediatrics
   Martin Cohen, MD
    Medical Officer, Division of Oncology Drug Products
   Jeff Summers, MD
    Medical Officer, Division of Biologic Oncology Products
   Anne Zajicek, MD, NIH
   Victoria Ferretti-Aceto, PharmD,              Executive Secretary
      Pediatric Initiatives

   Pediatric Research Equity Act, December 3, 2003

   Best Pharmaceuticals for Children Act, January
    4, 2002

    Both laws are intended to support and
    encourage drug development in the
    pediatric population
      Pediatric Research Equity Act

   One of two laws intended to promote the study of
    drugs and biologics in pediatric patients
      Studies prevent pediatric patients from being a

       “study of one”

   Studies in the pediatric population are REQUIRED,
    but only for the indication that was studied in adults
Best Pharmaceuticals for
Children Act (BPCA)
   In pediatric oncology
       prioritize new drugs for study
       assure timely access to new treatments
       develop pre-clinical models of pediatric
       Why both PREA and BPCA?

   Distinction between the scope of studies
    requested under BPCA and required under
   PREA specific to indication in submission
   BPCA can ask for “off-label” indications
   Open Public Hearing Speaker

       Sadhana Dhruvakumar
Director, Medical Products Testing
People for the Ethical Treatment of Animals
Animal Use in Drug Development
       Questions from NIH to the
Pediatric Subcommittee of the Oncologic
        Drug Advisory Committee

     What type of prioritization process
      should be used for deciding which off-
      patent drugs should be studied?
         What is the definition of health benefit?
              Number of patients affected
              Lack of other drugs that treat the disease
              Severity of the disease
   Are there other drugs that should be
       Antineoplastics
       Supportive Care
            Anti-emetics
            Anti-infectives
            Analgesics
       Other
Issues in post-marketing studies
for clofarabine (Clolar™)
   Feasibility of proposed populations
    (ALL, 1st or 2nd relapse) & primary
    endpoint (4 mo EFS)?
   Design’s likelihood to permit adequate
    assessment of clinical benefit?
   Can data generated in adults support
    efficacy in pediatric ALL patients?
Issues in post-marketing studies
for clofarabine (Clolar™)
   Adult populations & primary efficacy
    endpoints do not permit adequate
    assessment of clinical benefit. Suggest
    focus on 1st relapse, known active agents in
    controlled setting. Remission induction &/or
    MRD are potential primary endpoints.
   It is not plausible that Adult AML data
    supports efficacy in pediatric ALL patients
    based on current knowledge of disease
Issues in post-marketing studies
for pegfilgrastim (Neulasta®)

   Will Amgen’s study in patients with
    sarcoma treated with VAdriac/IE allow
    for extrapolation of activity and safety
    findings across all age groups and
    different pediatric cancers?
Issues in post-marketing studies
for pegfilgrastim (Neulasta®)

   Difficulty enrolling this population of
    patients (esp. younger ages) in these
   Difficulty administering filgrastim in
    randomized settings
   Competition with other studies where
    protocols demand growth factors
Issues in post-marketing studies
for pegfilgrastim (Neulasta®)

1. Patients serve as own controls
2. Randomize for the first cycle
3. Consider studies in patients with
   rhabdomyosarcoma & neuroblastoma
   to enhance age range of subjects
Issues in post-marketing studies
for palifermin (Kepivance®)
   Suitability & feasibility of need for dose
   Need for pharmacokinetic data
   Choice of patient population
    (homogenous Vs heterogeneous r/t
    underlying disease, source of stem
    cells, cytotoxic regimen, etc.)
      Issues in post-marketing studies
      for palifermin (Kepivance®)
   Need data from pediatric populations:
   Suggest decreasing # of doses tested in dose
    escalation portion
   Consider evaluating other schedules
   Suggest study in pts with acute leukemia receiving
    allogeneic transplant would be useful, feasible
   Population could be both autologous & allogeneic
    transplant recipients
   Use adult PK data as a guideline for when/how to
    sample, but only as a framework for ped dosing
Ongoing studies of vincristine
& actinomycin-D
   Approach to safety/efficacy & PK data
   Are there additional data that should be
   Could frequency of toxicity be minimized with
    dose cap?
   Would dose-capping cause underdosing &
    subsequent lack of efficacy
   Application of mathematical models for dose
Ongoing studies of vincristine
& actinomycin-D

   VCR: difficult to quantify toxicity
   Lack of standard assessments & scoring
    for peripheral neuropathy
   Required tests for measuring or
Off-patent BPCA Process
   Could additional labeling data to
    provide health benefits for pediatric
    patients r/t off-patent drugs and/or
    therapeutic drug classes?
    Off-patent BPCA Process
   Need dose adjustment guidelines for many
    off-patent drugs, specifically in obese children
   Administration methods to decrease toxicity –
    eg., less frequent dosing intervals
   Dose-optimization via systematic methods
   Tools to measure early toxicity
   Arbitrary age groups (suggesting 2 age
    ranges during first year of life, then 1-5 & 5-
     Suggested topics for future ODAC
     Pediatric Subcommittee Meetings
   Pain control
   Symptom management in neonates
   Drug delivery systems
   Long term sequelae
   Orphan drug indications
   End of life & palliative care
   Indications waived from the requirement
    for conducting pediatric studies
     Suggested topics for future ODAC
     Pediatric Subcommittee Meetings

   Role of stable disease as an endpoint
   Endpoints for pediatric cancer
   Pre-clinical predictors of clinical outcomes
   Re-formulations, rounding off errors
   Past 7 years (post PREA & BPCA): any
    changes in getting drugs to pediatric cancer
    patients earlier?
Suggested next meeting of ODAC
    Pediatric Subcommittee:
      First quarter 2006

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