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

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

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.

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

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)

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)

Recruitment Experience Demographics Median age (years) Participants68 (49-74) Non-participants 62 (42-78) Median prior therapies Participants3.5 (0-8) Non-participants3 (0-7)

Recruitment Experience Diagnosis 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)

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

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

Most Common Physician-Related Barriers Negative effect on doctor–patient relationship Belief that doctor should make decisions Feeling coerced to join Physicians attitude towards trial

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.