This phase I trial studies the side effects and best dose of veliparib in treating patients with malignant solid tumors that do not respond to previous therapy. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and recommended phase II dose of chronically dosed single-agent ABT-888 (veliparib) in patients with either a refractory breast cancer (BRCA) 1/2- mutated solid cancer; platinum-refractory ovarian, fallopian tube, or primary peritoneal cancer; or basal-like breast cancer. SECONDARY OBJECTIVES: 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 evaluable patients with germline BRCA mutations. II. To determine the effects of ABT-888 treatment on the level of poly ADP-ribose polymerase (PARP) inhibition and deoxyribonucleic acid (DNA) damage in peripheral blood mononuclear cells (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 anti-tumor response. OUTLINE: This is a dose-escalation study. Patients receive veliparib orally (PO) twice daily (BID)\* 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 pharmacodynamic studies. After completion of study therapy, patients are followed for 4 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
98
City of Hope Comprehensive Cancer Center
Duarte, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
City of Hope South Pasadena
South Pasadena, California, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States
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
Time frame: 28 days
Incidence of toxicities as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
The maximum grade of toxicity for each category of interest will be recorded for each patient and the summary results will be tabulated by category and grade. All DLTs and other serious (grade 3 or greater) will be described on a patient-by-patient basis; descriptions will include dose level and any relevant baseline data. Statistics on the number of cycles received by patients and any dose reductions will be tabulated.
Time frame: Up to 30 days post-treatment
Response (complete response, partial response, stable disease) evaluated using the Response Evaluation Criteria in Solid Tumors
Will be tabulated by disease diagnosis and by dose level.
Time frame: Up to 4 weeks post-treatment
Pharmacokinetic parameters
Time frame: Prior to taking veliparib on day 1, 4, and 15 then 30 minutes, 1 hour, 1½, 2, 3, 4, 6, and 8 hours after taking veliparib on day 1 and 15, and 24 hours after taking day 1 and day 15 doses of veliparib
Changes in PAR in PBMCs and tumor biopsies
Will be assessed with Wilcoxon signed rank tests.
Time frame: Baseline to 4 weeks post-treatment
Changes in gamma-H2A histone family, member X (H2AX) in PBMCs and tumor biopsies
Will be assessed with Wilcoxon signed rank tests.
Time frame: Baseline to 4 weeks post-treatment
Changes in BRCA 1/2 expression in tumor blocks
Comparisons of the expression levels in the two groups of patients will be made with Wilcoxon tests.
Time frame: Baseline to 4 weeks post-treatment
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.