an Expert: volume 2/spring 2007
Clinical Trials Joyce Ingold, RN, MSN, OCN.
Kim Johnke (KJ): What are Clinical Trials?
Joyce Ingold (JI): A clinical trial is a
“Ultimately, to bringclinical trial participants
potential new life-saving
research study in which human volunteers
treatments to other individuals facing cancer.
help investigators answer specific medical
questions. Treatment trials test for safety
staffed with a research nurse who keeps (where comparison is necessary) participants
and efficacy of investigational new drugs
(IND) for diseases and conditions. In the close track of patients. Because the IND is are randomized into treatment groups
United States, clinical trials are regulated being tested in humans, it is necessary to (trial arms), and the PI compares
by the National Institutes of Health (NIH) know every detail about the patient’s differences between groups. For example,
and Food and Drug Administration (FDA). experience. In the long-term, the data we one trial arm may receive the SOC, while
All drugs – whether over-the-counter or collect from participants in clinical trials another arm receives SOC therapy plus
prescription – must pass through clinical will help establish the minimum effective the IND. In this type of trial, all cancer
trials before receiving FDA approval and dosage, as well as which cancer(s) it will patients would receive the standard of care.
THE LUSTGARTEN FOUNDATION FOR PANCREATIC C ANCER RESEARCH
becoming available for public consumption. effectively treat. Ultimately, cancer clinical
trial participants are helping oncologists to KJ: Why are Clinical Trials particularly
As a form of research, clinical trials follow bring potential new life-saving treatments to important to people with pancreatic cancer?
an action plan called a protocol, which other individuals facing cancer.
is carefully designed by a principal JI: Unfortunately, pancreatic cancer is
investigator (PI) and approved by an KJ: How do Cancer Clinical Trials differ often detected after it has metastasized.
Institutional Review Board. Clinical from non-cancer Trials? The standard of care therapy for pancreatic
trials exist in all areas of medicine. cancer is Gemcitabine (Gemzar). To date,
JI: Generally, individuals are more likely Gemzar has increased survivability by a matter
KJ: How do Clinical Trials benefit individuals to participate in non-cancer clinical trials of months, and investigators want to improve
in the short-term and the long-term?
as first-line therapy, whereas cancer this rate. Therefore, many pancreatic cancer
JI: It is important to emphasize that clinical trials are usually reserved for when patients seek clinical trials as first-line treat-
patients do not need to join a clinical trial the cancer no longer responds to the ment. Scottsdale Healthcare offers first-line
to receive quality cancer care, and not all standard of care (SOC) therapy. Also, Phase I and II clinical trials for pancreatic
trials offer direct benefits to patients. At in quality cancer clinical trials, placebos cancer patients who have never received
Scottsdale Healthcare, we find that are usually not used. Be sure to ask your chemotherapy. Clinical trials are helping us
a short-term benefit of clinical trials is doctor whether a placebo will be used in a learn which other drugs can be combined
personalized care. Also, clinical trials are particular trial. In a cancer clinical trial, with Gemzar to improve survivability.
*Words in bold are defined in the glossary. (continued)
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an Expert: Cancer Clinical Trials
KJ: How does the Clinical Trials process KJ: What is meant by ‘accrual?’ and cooperate with staff, and to participate
work? in their health care decisions. Participants
JI: The sponsoring agency pre-determines also have a responsibility to disclose any
JI: The Clinical Trials process involves the total number of participants that a and all types of medications or drugs that
four distinct phases. Phase One brings trial will accommodate. The process of they are taking (including herbal, over the
an IND to humans, and the PI seeks to enrolling participants is called ‘accrual.’ counter and alcohol). They are also asked to
understand the safest dosage required. The accrual process works in phases, where promptly and honestly report unexpected
Phase One trials often include patients several participants are accrued together problems or concerns to the treatment team.
into a cohort. Cohorts are ‘mini-groups’
with various forms of cancer to learn which
tumor types have the most consistent
of participants who start a trial together KJ: Who comprises the ‘treatment team?’
and receive the same treatment dosage.
response to the IND. These early-phase JI: A host of professionals may comprise
trials usually involve small groups of Participants cannot move between cohorts a treatment team, including medical
volunteers (20-30) and last one to two during the study. For example, a patient oncologists, radiation oncologists, surgical
years. During Phase Two, the PI continues who starts a clinical trial drug at a dosage oncologists, pathologists, nurses, social
testing the safety of the IND and begins of 10 milligrams will receive this dosage workers, nutritionists, psychologists and
to evaluate how well the new drug works. until the cancer stops responding. If the more. The principal investigator (PI) is
Phase Two trials usually focus on a specific patient decides to leave the 10-milligram the physician who designs and conducts
type of cancer. This phase brings the drug cohort, s/he could enroll in a different the trial. In our office, we also have a Nurse
to a larger number of participants. trial, but could not skip to a new cohort Practitioner who functions as a primary
within the same trial. care provider in collaboration with clinic
Phase Three compares data from people physicians. Each clinical trial also has a
taking the IND with data from people KJ: What happens if, during the course of research nurse. This is the person with
receiving standard treatment. These trials a trial, a participants’ medical status drops whom participants typically develop
depend on large groups of volunteers below the baseline requirement? Could this a close rapport, because the research nurse
person remain in the trial? keeps a very close eye on study partici-
(up to 3,000) to confirm efficacy, monitor
side effects, compare commonly used pants. S/he will ask questions about issues
JI: We will do everything possible to keep such as diarrhea, eating habits, nausea,
treatments and collect information that a person eligible for a trial, including blood
will allow the IND to be used safely. pain, etc. A pharmacist assists in monitor-
transfusions and/or providing support to
The time frame for Phase Three trials is ing additional medications that an individ-
maintain performance status. If we cannot
usually several years. After Phase Three ual may be taking, such as antiemetics,
maintain an acceptable performance status,
trials are completed, the company may antidepressants and narcotics for pain.
then an individual would need to discon-
apply for FDA approval of the IND. Supportive services will often include a
tinue participation in the clinical trial.
social worker to help address various social,
Phase Four trials represent the final phase KJ: What are the rights and responsibilities emotional and financial concerns.
of the trials process, and are conducted of Clinical Trial participants?
KJ: What happens if, for any reason,
after the treatment has been FDA
JI: Every clinical trial participant has a Bill a clinical trial is discontinued? Can the
approved. Phase Four trials seek to
of Rights, which includes receiving a copy patient continue to receive the IND?
ensure that the newly approved drug
of the signed informed consent docu-
is indeed effective. JI: A clinical trial may be stopped when
ment. Informed consent is the process by
which potential trial participants learn key data overwhelmingly demonstrates a
KJ: Can anybody join a Clinical Trial? benefit to the IND and the trial sponsor
facts, including potential risks and benefits
(See Box) before deciding whether to join. proceeds to FDA application. A trial
JI: Every clinical trial has eligibility could also be stopped because it’s not
criteria and inclusion/exclusion The process includes reviewing a document
that explains key details of the study, contact demonstrating a benefit. If an individual’s
criteria; these criteria ensure that clinical trial is discontinued, s/he can
information, and required procedures
researchers are comparing ‘apples to apply for continued/compassionate use
(patient responsibilities). The document is
apples.’ Patients must also meet a of the study drug, or begin a new clinical
not a contract, and participants may leave a
performance status requirement to trial after meeting a new set of eligibility
study at any time, and for any reason.
be part of a clinical trial. Examples of criteria. Between clinical trials, however,
performance status criteria include, but In order to preserve the quality of the there is a ‘wash-out’ period lasting roughly
are not limited to, various blood values, research data, trial participants are 28 days. This refers to a required time
kidney and liver function, and activities asked to provide honest and complete period from the last day of treatment
of daily living (ADL). information, to comply with the protocol before a new treatment can begin.
2 www.lustgartenfoundation.org | THE LUSTGARTEN FOUNDATION FOR
KJ: Would a study participant eventually KJ: Are there additional considerations KJ: Do you have any final thoughts about the
‘complete’ a trial? What are end-points? before joining a trial? role of clinical trials in pancreatic cancer?
JI: Every trial participant is evaluated at JI: Motivation to join a clinical trial is JI: I think it is important that no patient
set times (ex., every six to eight weeks) patient-specific. Some people will remain ever feel abandoned. Even if a patient is not
with various tests. If it is determined that on clinical trials because they feel it’s eligible for clinical trials, we can provide
the cancer has progressed, they may not important to take an active role in their standard of care treatment and/or palliative
be continued on the trial. Instead, we will health care. Others feel one trial is all support to improve quality of life. In my
work to find another. If at that evaluation they can do. Many personal lifestyle opinion, there’s always something ‘more’ to
point, we find that the disease either has factors and individual preferences need do. New clinical trials open every day, and
not progressed or has regressed, we will to be considered by patients wishing to it never hurts to ask whether there is
continue their participation on the trial determine whether a trial is the right something ‘more.’
until the next evaluation period. I know course of action. People often ask me, FIND CANCER CLINICAL TRIALS
people who have been on a clinical trial “How do I know if I should try a clinical
The Lustgarten Foundation
for years (even after the trial has closed trial?” My answer is, “You don’t know Clinical Trial Matching Service
to accrual) because they demonstrate no until you start investigating the trial.” With EmergingMed
The key is that patients should do what 1-800-535-1867
disease progression. End-points refer to www.lustgarten.org
the parameters that will be measured to they feel is best for them.
evaluate the research study’s objectives.
KJ: How are Cancer Clinical Trials funded, Potential Benefits & Risks of
and are there any costs to participants?
Participating in Cancer Clinical Trials
JI: The federal government is the nation’s BENEFITS RISKS
largest sponsor of clinical trials. Cancer
clinical trials may also be sponsored by ✓ Gaining early access to potential new ✓ Possibility of unexpected side effects
treatments for pancreatic cancer from the experimental drug
drug companies, private agencies, and/or
by institutions themselves. Each insurance ✓ Being an ‘informed consumer’ and ✓ New treatments do not necessarily
taking an active role in your health care offer greater benefit than the
company is different, and patients should standard of care
check with their individual carriers for ✓ Receiving individualized attention
and close monitoring by an expert ✓ Possibility of added time and costs
specific rules and guidelines regarding clinical
treatment team (ex., travel, housing, expenses not
trial coverage. Typically, insurance covers covered by insurance) for patients
SOC therapy administered throughout the ✓ Potential for the experimental drug
to provide greater benefit than the
clinical trial, and the trial sponsor covers standard of care
non-standard care. Advocacy resources
✓ Helping to advance medical treatments
(See Box) are available to assist patients for all pancreatic cancer patients
in understanding their insurance rights.
Bill of Rights for Clinical Trial Volunteers
Cancer Clinical Trials ✓ To be told the purpose of the clinical trial ✓ To be allowed to ask any questions about
www.shc.org the trial before giving consent and at any
✓ To be told all the risks, side effects or
time during the course of the study
National Cancer Institute discomforts that might be reasonably
1-800-4-CANCER expected ✓ To be allowed ample time, without
www.cancer.gov pressure, to decide whether to consent
✓ To be told of any benefits that can be
or not to consent to participate
Patient Advocate Foundation reasonably expected
1-800-532-5274 ✓ To refuse to participate, for any reason,
✓ To be told what will happen in the study
www.patientadvocate.org before and after the trial has started
and whether any procedures, drugs or
Center for Information & Study on devices are different than those that are ✓ To receive a signed and dated copy of
Clinical Research Participation used as standard medical treatment the informed consent form
1-888-CISCRP3 ✓ To be told about options available and ✓ To be told of any medical treatments
www.ciscrp.org how they may be better or worse than available if complications occur during
Informed Consent:The Consumer’s Guide to the being in a clinical trial the trial
Risks and Benefits of Volunteering for Clinical Trials.
By Kenneth Getz & Deborah Borfitz Source: Getz, K., & Borfitz, D. (2002). Informed Consent. Boston, MA:Thomson CenterWatch
PANCREATIC C ANCER RESEARCH | 1111 Stewart Avenue • Bethpage, NY 11714 | 516-803-2304 3
Antiemetic – A drug used (or tending to) First-line Therapy – The first type of therapy
Performance Status – The performance status
prevent or check vomiting. given for a condition or disease. semi-quantifies the ability of a patient to perform
daily activities.This semi-quantification is very
Cohort – A group of individuals with some Inclusion/Exclusion Criteria – The medical helpful in clinical trials in assessing the state of
characteristics in common. standards determining whether a person may or health of patients under treatment.The performance
Compassionate Use – A method of providing may not be allowed to enter a clinical trial.These status also plays a role in determining whether a
experimental therapeutics prior to final FDA criteria are based on such factors as age, gender, patient can tolerate intensive therapy.
approval for use in humans.This procedure is the type and stage of a disease, previous treat-
used with very sick individuals who have no Placebo – An inert or innocuous substance used
ment history, and other medical conditions. It is
other treatment options. Often, case-by-case especially in controlled experiments testing the
important to note that inclusion and exclusion efficacy of another drug.
approval must be obtained from the FDA for criteria are not used to reject people personally,
“compassionate use” of a drug or therapy. but rather to identify appropriate participants Principal Investigator – The individual who has
Dose – The measured quantity of a therapeutic and keep them safe. primary responsibility for designing the protocol,
agent to be taken at one time. selecting the investigation team, carrying out the
Informed Consent – The process of learning scientific investigation, and reporting the results.
Efficacy – The maximum ability of a drug or the key facts about a clinical trial before deciding
treatment to produce a result regardless of Protocol – A detailed plan of a scientific/medical
whether or not to participate. It is also a continuing
dosage. A drug passes efficacy trials if it is effective experiment, treatment, or procedure.
process throughout the study to provide informa-
at the dose tested and against the illness for tion for participants.To help someone decide Randomization – Process that reduces the
which it is prescribed. In the procedure mandated likelihood of bias by assigning people to treatment
whether or not to participate, the doctors and
by the FDA, Phase II clinical trials gauge efficacy, groups by chance alone (randomly).When groups
and Phase III trials confirm it. nurses involved in the trial explain the details of
the study. are created by random assignment, individual
Eligibility Criteria – The clinical and demographic characteristics are less likely to make the results
characteristics that define which persons are Institutional Review Board (IRB) – A committee inaccurate.
eligible to be enrolled in a trial. of physicians, statisticians, researchers, community Research Study – Investigation or experimentation
advocates, and others that ensures that a clinical aimed at the discovery and interpretation of facts,
End Points – Overall outcome that the protocol
trial is ethical and that the rights of study partici- revision of accepted theories or laws in the light
is designed to evaluate. Common endpoints are
toxicity, disease progression, remission, complete pants are protected.All clinical trials in the US of new facts, or practical application of such new
response, partial response, etc. must be approved by an IRB before they begin. or revised theories or laws.
FDA Approval – In the U.S., the Food and Drug Investigational New Drug – A new drug, antibiotic Standard of Care – Treatment regimen or medical
Administration (FDA) must approve a substance drug, or biological drug that is used in a clinical management based on state-of-the-art patient care.
as a drug before it can be marketed.The approval investigation. It also includes a biological product Treatment Trials – Refers to trials which test
process involves several steps including pre-clinical used in vitro for diagnostic purposes. new treatments, new combinations of drugs, or
laboratory and animal studies, clinical trials for new approaches to surgery or radiation therapy.
safety and efficacy, filing of a New Drug Metastasis – The spread of a disease-producing
Application by the manufacturer of the drug, agency (such as cancer cells or bacteria) from the Trial Arm – Any of the treatment groups in a
FDA review of the application, and FDA initial or primary site of disease to another part randomized trial. Most randomized trials have two
approval/rejection of application. of the body. "arms," but some have three "arms," or even more.
Sources: Clinicaltrials.gov and MedLinePlus
an Expert: About The Lustgarten Foundation
contributor The Lustgarten Foundation For Pancreatic
Cancer Research is a non-profit organization
In addition to its research funding activities,
The Lustgarten Foundation provides
dedicated to advancing the diagnosis, comprehensive patient information
JOYCE INGOLD, RN, MSN, OCN
treatment, cure and prevention of this materials at no cost to patients and the
Joyce Ingold serves as Patient Care disease.The Foundation was named for professionals who serve them.
Coordinator for TGen Clinical Research Marc Lustgarten,Vice Chairman of
Cablevision Systems Corporation, who For additional information on the work
Services (TCRS), located at Scottsdale
was diagnosed with pancreatic cancer. of The Lustgarten Foundation, visit
Healthcare. Joyce is an Oncology Certified www.lustgarten.org
Nurse with more than 21 years of experience. The Lustgarten Foundation concentrates on
She is a member of the National Oncology stimulating the scientific community to conduct Supported by an educational grant from
the research necessary to find a cure for
Nursing Society, Phoenix Oncology
pancreatic cancer.Today,The Lustgarten
Nursing Society, and the American Foundation is the nation’s largest private
Nursing Association. supporter of pancreatic cancer research.
1111 Stewart Avenue
ask Bethpage, NY 11714
an Expert: 516-803-2304