A PHASE I STUDY OF INTRAVENOUS CARBOPLATIN/PACLITAXEL OR INTRAVENOUS AND INTRAPERITONEAL PACLITAXEL/CISPLATIN IN COMBINATION WITH CONTINUOUS OR INTERMITTENT/ CTEP-SUPPLIED AGENT ABT-888 (NSC #737664) AND CTEP-SUPPLIED AGENT BEVACIZUMAB (NSC #704865) IN NEWLY DIAGNOSED PATIENTS WITH PREVIOUSLY UNTREATED EPITHELIAL OVARIAN, FALLOPIAN TUBE OR PRIMARY PERITONEAL CANCER
I. To determine the maximum tolerated dose (MTD) and dose-limiting toxicities of ABT-888
when administered with carboplatin, paclitaxel, and bevacizumab using 2 different treatment
regimens in patients with newly diagnosed stage II-IV ovarian epithelial, fallopian tube, or
primary peritoneal cancer.
II. To determine the feasibility of these regimens over 4 courses once the MTD is
III. To assess the toxicity of these regimens using NCI CTCAE v4.0 criteria.
I. To estimate the response rate in patients with measurable disease. II. To estimate the
progression-free survival of patients treated with these regimens.
III. To assess the extent of poly-ADP-ribose polymerase (PARP) inhibition in peripheral
blood mononuclear cells on day 1 of courses 1 and 2.
IV. To assess genomic BRCA mutation status in all patients and descriptively correlate it
with toxicity and efficacy.
OUTLINE: This is a multicenter, dose-escalation study of ABT-888 followed by a feasibility
study. Patients are sequentially assigned to 1 of 2 treatment regimens.
REGIMEN I: Patients receive paclitaxel 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
oral ABT-888 twice daily 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 ABT-888 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. Blood samples are collected periodically for biomarker analysis.
After completion of study treatment, patients are followed up periodically.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicities (DLTs) occurring in the first or second course of treatment (dose-escalation phase)
Up to day 42
Gynecologic Oncology Group
United States: Food and Drug Administration
|Johns Hopkins University||Baltimore, Maryland 21205|
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|
|Cleveland Clinic Foundation||Cleveland, Ohio 44195|
|University of Iowa Hospitals and Clinics||Iowa City, Iowa 52242|
|Washington University School of Medicine||Saint Louis, Missouri 63110|
|Fox Chase Cancer Center||Philadelphia, Pennsylvania 19111|
|Franklin Square Hospital Center||Baltimore, Maryland 21237|
|University of Oklahoma Health Sciences Center||Oklahoma City, Oklahoma 73104|
|University of Wisconsin Hospital and Clinics||Madison, Wisconsin 53792-0001|
|MetroHealth Medical Center||Cleveland, Ohio 44109|
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center||Columbus, Ohio 43210-1240|
|University of Virginia||Charlottesville, Virginia 22908|
|Case Western Reserve University||Cleveland, Ohio 44106|
|Riverside Methodist Hospital||Columbus, Ohio 43214|
|Virginia Commonwealth University||Richmond, Virginia|
|Hillcrest Hospital Cancer Center||Mayfield Heights, Ohio 44124|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|Women and Infants Hospital||Providence, Rhode Island 02905|
|University of Colorado Cancer Center - Anschutz Cancer Pavilion||Aurora, Colorado 80045|
|Georgia Health Sciences University||Augusta, Georgia 30912|
|Gynecologic Oncology Group||Philadelphia, Pennsylvania 19103|