This phase I trial studies the side effects and best dose of veliparib when given together with carboplatin, paclitaxel, and bevacizumab in treating patients with newly diagnosed stage II-IV ovarian epithelial, fallopian tube, or primary peritoneal cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cells to repair themselves from damage and survive. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab, a type of drug called a monoclonal antibody, blocks tumor growth by targeting certain cells and preventing the growth of new blood vessels that tumors need to grow. Giving veliparib together with carboplatin, paclitaxel, and bevacizumab may kill more tumor cells.
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and dose-limiting toxicities of ABT-888 (veliparib) when administered using continuous versus intermittent dosing schedules with intravenous carboplatin, paclitaxel and bevacizumab using two different treatment regimens; or with intraperitoneal cisplatin and intravenous and intraperitoneal paclitaxel and bevacizumab in women with newly diagnosed, previously untreated, epithelial ovarian, fallopian tube, or primary peritoneal cancer. II. To determine the feasibility of these treatment regimens over four cycles in a 2-stage group sequential design once the MTD is established. III. To assess the toxicity of these regimens using Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. SECONDARY OBJECTIVES: I. To estimate the response rate (in measurable disease patients) and progression-free survival in patients treated with these treatment regimens. TERTIARY OBJECTIVES: I. To assess the extent of poly-ADP-ribose polymerase (PARP) inhibition in peripheral blood mononuclear cells (PBMCs) on day 1 of cycles 1 and 2. II. To assess genomic breast cancer, early onset (BRCA) mutation status in all patients in regimens I and II with continuous ABT-888 dosing and descriptively correlate with toxicity and efficacy. OUTLINE: This is a dose-escalation study of veliparib followed by a feasibility study. Patients are sequentially assigned to 1 of 3 treatment regimens. REGIMEN I: Patients receive paclitaxel intravenously (IV) over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes (beginning in course 2) on day 1. Patients also receive veliparib orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for 6 courses. Patients then receive bevacizumab alone on day 1. Treatment with bevacizumab repeats every 21 days for 16 courses in the absence of disease progression or unacceptable toxicity. REGIMEN II: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15. Patients also receive carboplatin, bevacizumab, and veliparib as in Regimen I. Treatment repeats every 21 days for 6 courses. Patients then receive bevacizumab alone on day 1. Treatment with bevacizumab repeats every 21 days for 16 courses in the absence of disease progression or unacceptable toxicity. REGIMEN III: Patients receive paclitaxel IV over 3 hours on day 1 and intraperitoneally (IP) on day 8, and cisplatin IP on day 1 or 2. Patients also receive bevacizumab and veliparib as in Regimen I. Treatment repeats every 21 days for 6 courses. Patients then receive bevacizumab alone on day 1. Treatment repeats every 21 days for 16 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
431
Given IV
Given IV
Given IP
Correlative studies
Given IV or IP
Given PO
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
University of Colorado Hospital
Aurora, Colorado, United States
Augusta University Medical Center
Augusta, Georgia, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
MedStar Franklin Square Medical Center/Weinberg Cancer Institute
Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Washington University School of Medicine
St Louis, Missouri, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
...and 13 more locations
Incidence of dose-limiting toxicities (DLTs) occurring in the first or second course of treatment (dose-escalation phase)
Time frame: Up to day 42
Incidence of DLTs occurring in the first 4 courses of treatment (feasibility phase)
Time frame: Up to day 84
Objective tumor response (complete and partial response) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)
Tabulated by regimen and BRCA mutation status.
Time frame: Up to 11 years
Progression-free survival
Summarized using Kaplan-Meier plots by BRCA mutation status.
Time frame: Time from start of treatment to time of progression or death, assessed up to 11 years
Incidence of toxicity, graded according to National Cancer Institute CTCAE version 4.0
Tabulated by regimen and by BRCA mutation status.
Time frame: Up to 30 days after last dose of treatment
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.