Recruitment experience in a phase 0 trial of ABT-888, an inhibitor of poly (ADP-ribose) polymerase (PARP), in patients (pts) with advanced malignancies

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Abstract
14111 Background: Phase 0 trials conducted under the FDA Exploratory IND Guidance involve limited exposures to study drug with no expectation of clinical benefit. We present our experience in recruiting pts to a Phase 0 study of ABT-888, the first to be conducted at the NCI. Methods: Objective: To determine the ABT-888 dose that inhibits PARP in PBMCs and tumor after a single oral administration. Tumor biopsies at baseline and 3–6 hrs post drug were planned once PARP activity inhibition in PBMCs or target plasma Cmax was achieved. Protocol was approved by the NCI scientific committee, IRB, and CTEP, and was reviewed by the NIH Ethics Committee. Informed consent included an explicit statement acknowledging the non-therapeutic, non-personal benefit nature of the study. Results: Since 6/06, 17 pts screened; 6 enrolled. Reasons for declining participation: Non-therapeutic study (2); biopsy requirement (2); recommendation by oncologist (2) or family member (2); condition requiring treatment (3). Reasons for participation: Altruism (4); altruism + waiting for another study (2). Of 6 pts enrolled, colon cancer (2), lymphoma (2), carcinoid (1), lung cancer (1). Median age: Participants (P) 57 (49–64) and non-participants (NP): 62 (42–78). Median prior therapies: P 3.6 (0–8) and NP: 3 (0–7). Referral origin for P: Prior participation on NCI studies (2), prior pt-NCI physician relationship (4). Ethnicity of P: White (5) and Hispanic (1). 3 of 6 pts underwent serial biopsies as required by protocol. Conclusion: Phase 0 recruitment is feasible and the accrual can be completed in a timely fashion, but depends on pt altruism and prior physician-pt relationship. These studies can be ethically conducted provided that interventions are of minimal risk, the study experience is commensurate with pt expectations, and that results are invaluable to subsequent pts. No significant financial relationships to disclose.

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