A Phase 0 Pharmacokinetic, Pharmacodynamic Study of ABT-888, an Inhibitor of Poly (ADP-ribose) Polymerase (PARP), in Refractory Solid Tumors and Lymphoid Malignancies
- Determine the dose-range at which ABT-888 inhibits poly (ADP-ribose) polymerase (PARP)
in tumor samples and in peripheral blood mononuclear cells (PBMCs) in patients with
refractory solid tumors or lymphoid malignancies.
- Determine the pharmacokinetics of ABT-888.
- Determine the time course of PARP inhibition in PBMCs by ABT-888.
- Determine the safety of administering 1 dose of ABT-888 in these patients.
OUTLINE: This is a dose-finding study.
Patients receive oral ABT-888 once on day 1.
Cohorts of 3 patients receive escalating doses of ABT-888 until significant tumor poly
(ADP-ribose) polymerase (PARP) inhibition is observed in 3 of 3 patients at 2 dose levels.
Significant PARP inhibition is defined as ≥ 0.69 reduction on the log scale in poly
(ADP-ribose) level from baseline to 3-6 hours after ABT-888 administration (with 90%
confidence that it is not due to chance variation).
Patients undergo peripheral blood collection at baseline and periodically after ABT-888
administration for PARP inhibition, pharmacokinetic, and pharmacodynamic studies. Once
significant PARP inhibition is observed in 1 of 3 patients, subsequently enrolled patients
also undergo tumor biopsy* at baseline and 3-6 hours or 21-27 hours after ABT-888
administration to determine PARP inhibition in tumor tissue.
NOTE: *Patients with chronic lymphocytic leukemia undergo peripheral blood collection
instead of biopsy.
After completion of ABT-888 administration, patients are followed for 7 days.
PROJECTED ACCRUAL: A total of 23 patients will be accrued for this study.
Masking: Open Label, Primary Purpose: Treatment
Change in tumor poly (ADP-ribose) (PAR) levels from baseline to 3-6 hours after ABT-888 administration
Shivaani Kummar, MD
NCI - Medical Oncology Branch
United States: Food and Drug Administration
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office||Bethesda, Maryland 20892-1182|