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

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?

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

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

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

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 x-rays or radioactive substances

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 one’s 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

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

Clinical Trial Protocol A written, detailed action plan that: Provides background about the trial Specifies trial objectives Describes trial’s design and organization Ensures that trial procedures are consistently carried out

Investigational Drug Use Outside of a Clinical Trial Group C drugs Treatment Investigational New Drug application Compassionate use program

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 intervention’s effectiveness

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)

Randomization

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

Stratification

The Final Step: FDA Approval Review of New Drug Application (NDA) or Biologics License Application (BLA) Labeling Continued monitoring Feedback

Releasing the Results of Clinical Trials Peer-reviewed journals Public announcements Results not made public until end of trial

Improving Cancer Prevention, Detection, and Treatment Once proven safe and effective in a clinical trial, an intervention may become the new standard of care

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

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

Government Oversight of Safeguards for Participants Office for Human Research Protections (OHRP) The Common Rule FDA Regulations

Protecting Participants Before a Trial Scientific review by sponsoring organization Institutional review board approval Informed consent

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

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 patient’s care Believe that standard therapy is best Believe that clinical trials are more work Harbor concerns about the patient’s care or how the person will react to suggestion of clinical trial participation

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

Benefits of Participating in Clinical Trials Early access to new treatments Active role in own health care Participation in advancing medical knowledge

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

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

Referring Patients to Clinical Trials Health care professionals should know: Trial objectives Eligibility criteria Treatment and prevention options

Locating NCI Clinical Trials in the Community NCI clinical trial registry: Nation’s most comprehensive resource on cancer clinical trials www.cancer.gov 1-800-4-CANCER (1-800-422-6237)