A Phase 1 Study of Chronically-Dosed, Single-Agent ABT-888 in Patients With Either BRCA 1/2 -Mutated Cancer; Platinum-Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer; or Basal-Like Breast Cancer
I. To establish the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of
chronically dosed single-agent ABT-888 (veliparib) in patients with either a refractory BRCA
1/2- mutated solid cancer; platinum- refractory ovarian, fallopian tube, or primary
peritoneal cancer; or basal-like breast cancer.
I. To establish the safety and tolerability of single-agent ABT-888 in the above patient
population. A dose expansion at the recommended phase II dose will be performed in 6-12
patients with germline BRCA mutations.
II. To determine the effects of ABT-888 treatment on the level of PARP inhibition and DNA
damage in PBMCs and tumor samples or cells in malignant ascitic fluid III. To determine the
pharmacokinetics (PK) of chronically dosed ABT-888. IV. To document any evidence of
OUTLINE: This is a multicenter study.
Patients receive veliparib* orally (PO) daily on days 1-28. Courses repeat every 28 days in
the absence of disease progression or unacceptable toxicity.
NOTE: *Patients receive veliparib once on day 1 of course 1 for pharmacokinetic and
Blood samples are collected periodically for pharmacokinetic and pharmacodynamic studies.
Samples are analyzed for plasma concentrations of veliparib by LC-MS; PARP inhibition
levels; and γ-H2AX. Skin and hair samples may also be collected.
After completion of study therapy, patients are followed for 4 weeks.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD, DLT, recommended phase II dose of chronically dosed single-agent veliparib in patients with either a refractory BRCA 1/2- mutated solid cancer; platinum- refractory ovarian, fallopian tube, or primary peritoneal cancer; or basal-like breast cancer
University of Pittsburgh
United States: Food and Drug Administration
|Cancer Institute of New Jersey||New Brunswick, New Jersey 08901|
|City of Hope||Duarte, California 91010|
|University of Pittsburgh||Pittsburgh, Pennsylvania 15261|
|UC Davis Comprehensive Cancer Center||Sacramento, California 95817|
|University of Southern California||Los Angeles, California 90033|
|Penn State Milton S Hershey Medical Center||Hershey, Pennsylvania 17033|
|City of Hope- South Pasadena Cancer Center||South Pasadena, California 91030|