1. Cancer Clinical Trials:
In-Depth Information

2. 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

3. Phases of Clinical Trials
Phase 1: 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?

4. 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

5. Types of Clinical Trials
Treatment
Prevention
Screening and early detection
Diagnostic
Genetics
Quality-of-life / supportive care

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

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

14. 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

15. 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)

16. Randomization

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

18. Stratification

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

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

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

22. 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

23. 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

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

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

26. 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

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

28. 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

29. 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

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

31. 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

32. 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

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

34. Locating NCI Clinical Trials in the Community
NCI clinical trial registry:
Nation’s most comprehensive resource on cancer clinical trials
CANCER ( )