Cancer Clinical Trials:

In-Depth Information

The Drug Development and Approval Process

1. Early research and preclinical testing 2. IND application filed with FDA 3. Clinical trials (phases 1, 2, and 3) 4. NDA filed with FDA 5. FDA validates claim and approves drug
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Phases of Clinical Trials

Phase 1: 15-30 people
What dosage is safe? How should treatment be given? How does treatment affect the body?

Phase 2: Less than 100 people

Does treatment do what it is supposed to? How does treatment affect the body?
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Phases of Clinical Trials

Phase 3: From 100 to thousands of people
Compare new treatment with current standard

Phase 4: From hundreds to thousands of people

Usually takes place after drug is approved Used to further evaluate long-term safety and effectiveness of new treatment

Types of Clinical Trials

Treatment Prevention Screening and early detection Diagnostic Genetics Quality-of-life / supportive care
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Treatment Trials
Test safety and effectiveness of new agents or interventions in people with cancer Possible benefit:
Early access to new treatments

Possible risk:
Occurrence of unknown side effects
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Prevention Trials
For people at risk of developing cancer Action studies vs. agent studies Possible benefit:
Early access to new interventions

Possible risk:
Unknown side effects and effectiveness
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Screening and Early-Detection Trials

Assess new means of detecting cancer earlier in healthy people Possible benefit:
Detecting disease at an earlier stage, resulting in improved outcomes

Possible risks:
Discomfort and inconvenience If imaging technique is studied, exposure to xrays or radioactive substances
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Diagnostic Trials
Develop better tools for classifying types and phases of cancer and managing patient care Possible benefits:
New technology may be better and less invasive Earlier detection of recurrences

Possible risk:
May require people to take multiple tests

Genetics Trials
These trials seek to:
Determine how ones genetic makeup can influence detection, diagnosis, prognosis, and treatment Broaden understanding of causes of cancer Develop targeted treatments based on the genetics of a tumor
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Quality-of-Life / Supportive Care Trials

Aim to improve quality of life for patients and their families Possible benefit:
Early access to new treatment

Possible risk:
May not benefit from participation
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Clinical Trial Protocol

A written, detailed action plan that: Provides background about the trial Specifies trial objectives Describes trials design and organization Ensures that trial procedures are consistently carried out
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Investigational Drug Use Outside of a Clinical Trial

Group C drugs Treatment Investigational New Drug application Compassionate use program

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Clinical Trial Design

Eligibility criteria: Can range from general (age, sex, type of cancer) to specific (prior treatment, tumor characteristics, blood cell counts, organ function); eligibility criteria also vary with trial phase
Varies with protocol and phases

Endpoint: Measurable outcome that indicates an interventions effectiveness

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Clinical Trial Design

Randomization: A method used to prevent bias in research; a computer or a table of random numbers generates treatment assignments, and participants have an equal chance to be assigned to one of two or more groups (e.g., the control group or the investigational group)

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Randomization

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Clinical Trial Design

Stratification: Categorizing subjects into subgroups by specific characteristics
Enables researchers to look into separate subgroups to see whether differences exist

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Stratification

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The Final Step: FDA Approval

Review of New Drug Application (NDA) or Biologics License Application (BLA) Labeling Continued monitoring Feedback

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Releasing the Results of Clinical Trials

Peer-reviewed journals Public announcements
Results not made public until end of trial

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Improving Cancer Prevention, Detection, and Treatment

Once proven safe and effective in a clinical trial, an intervention may become the new standard of care

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Advancing Cancer Care

Gleevec for chronic myelogenous leukemia Cervical cancer: improved survival rates Breast cancer: less extensive surgery Intron-A for melanoma Biological therapy Monoclonal antibodies Cancer vaccines
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Evolution of Participant Protection

Nuremberg Tuskegee Syphilis Study National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research Belmont Report National Research Act
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Government Oversight of Safeguards for Participants

Office for Human Research Protections (OHRP)
The Common Rule

FDA Regulations

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Protecting Participants Before a Trial

Scientific review by sponsoring organization Institutional review board approval Informed consent

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Protecting Participants During a Clinical Trial

Institutional review boards (IRBs) Data and safety monitoring boards (DSMBs)
Minimize risks Ensure integrity of data Can stop study if necessary

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Barriers to, Benefits of, and Risks of Participation in Clinical Trials

Barriers to Adult Participation in Clinical Trials

Physicians and other health professionals may: Be unaware of appropriate trials Be unwilling to lose control of patients care Believe that standard therapy is best Believe that clinical trials are more work Harbor concerns about the patients care or how the person will react to suggestion of clinical trial participation

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Barriers to Adult Participation in Clinical Trials

Patients may: Be unaware of clinical trials Lack access to trials Fear, distrust, or be suspicious of research Have practical or personal obstacles Face insurance or cost problems Be unwilling to go against their physicians wishes

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Benefits of Participating in Clinical Trials

Early access to new treatments Active role in own health care Participation in advancing medical knowledge

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Risks of Participating in Clinical Trials

New treatments are not always better than standard care Unexpected side effects May not work for everyone Additional cost
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NCI-Sponsored Clinical Trial Programs

Clinical Trials Cooperative Group Program Clinical Trials Support Unit (CTSU) Community Clinical Oncology Program (CCOP) Minority-Based Community Clinical Oncology Program Cancer Centers Program Clinical Grants Program
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Referring Patients to Clinical Trials

Health care professionals should know: Trial objectives Eligibility criteria Treatment and prevention options

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Locating NCI Clinical Trials in the Community

NCI clinical trial registry:

Nations most comprehensive resource on cancer clinical trials www.cancer.gov 1-800-4-CANCER (1-800-422-6237)
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