Martin E' Gutierrez, MD

1
Recruitment Experience in a Phase 0 Trial of
ABT-888, an Inhibitor of Poly (ADP-ribose)
Polymerase (PARP), in Patients With Advanced
Malignancies

• Martin E. Gutierrez, MD

2
Recruitment of Patients for Clinical Trials

• Enrolling participants onto cancer clinical
  trials presents an important challenge
• Only about 3 of adult patients with cancer
  participate in clinical trials
• Barriers to participation in clinical trials
• Protocol-related
• Patient-related
• Physician-related
• Recruitment for a Phase 0 trial is particularly
  challenging

3
Recruitment Experience in a Phase 0 Study

• Phase 0 trials conducted under the FDA
  Exploratory IND Guidance involve limited
  exposures to study drug with no expectation of
  clinical benefit.
• Protocol was approved by the NCI scientific
  committee, IRB, and CTEP, and was reviewed by the
  NIH Ethics Committee.
• Informed consent included Explicit statement
  acknowledging the non-therapeutic, non-personal
  benefit nature of the study.

4
Recruitment Experience 6/06 - 8/07

• 24 patients screened 14 enrolled
• Referral Origin
• Prior participation in NCI studies (9)
• Prior patient-NCI physician relationship (5)
• Reasons for Participation
• Altruism (6)
• Altruism waiting for another study (8)
• Biopsies
• 9 of 14 patients underwent serial biopsies
• as required by protocol

5
Recruitment Experience Reasons for Declining
Participation

• Non-therapeutic study (2)
• Biopsy requirement (2)
• Recommendation (4)
• Local oncologist (2)
• Family member (2)
• Condition requiring treatment (2)

6
Recruitment Experience Demographics

• Ethnicity
• Participants
• White (11)
• Hispanic (1)
• African American (2)
• Non-Participants
• White (6)
• Hispanic (1)
• African American (3)

• Gender
• Participants
• Male (11)
• Female (3)
• Non-Participants
• Male (7)
• Female (3)

7
Recruitment Experience Demographics

• Median age (years)
• Participants 68 (49-74)
• Non-participants 62 (42-78)
• Median prior therapies
• Participants 3.5 (0-8)
• Non-participants 3 (0-7)

8
Recruitment ExperienceDiagnosis

• Adenocarcinoma
• Colorectal cancer (2)
• Anexal (1)
• Non-Hodgkins lymphoma
• B-cell NHL (4)
• T-cell NHL (2)
• Squamous cell carcinoma
• Head neck (1)
• Rectum (1)
• Carcinoid (1)
• Small cell lung cancer (1)
• Melanoma (1)

9
Most Common Protocol-Related Barriers

• Concerns with the trial setting
• Dislike of randomization
• General discomfort with the research process
• Complexity and stringency of the protocol
• Presence of a placebo or no-treatment group
• Potential side-effects
• Being unaware of trial opportunities
• The idea that clinical trials are not appropriate
  for serious diseases
• Fear that trial involvement would have a negative
  effect on the relationship with their physician
• Fear that trial involvement would preclude future
  participation in other studies

10
Most Common Patient-Related Barriers

• Concerns over costs or health insurance
• Transport or distance to trial site
• Lack of family support or increased anxiety
• Uncomfortable with experimentation
• Do not want to lose control of decision-making
  
• Feelings of uncertainty
• Quality of life might be reduced
• Fear or mistrust of research or researchers
• Religious or cultural factors and fear of
  discrimination

11
Most Common Physician-Related Barriers

• Negative effect on doctorpatient relationship
  
• Belief that doctor should make decisions
• Feeling coerced to join
• Physicians attitude towards trial

12
Recruitment Experience Conclusion

• Phase 0 recruitment is feasible but depends on
  patients altruism and prior physician-patient
  relationship.
• These studies can be ethically conducted and
  accrual completed in a timely fashion provided
  that interventions are of low risk, the study
  experience is commensurate with patients
  expectations, and that results are invaluable to
  subsequent patients.