This phase I clinical trial studies the side effects and best dose of veliparib when given together with paclitaxel and cisplatin and to see how well they work in treating patients with cervical cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment or that has come back. Drugs used in chemotherapy, such as paclitaxel and cisplatin, 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. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving more than one drug (combination chemotherapy) and giving chemotherapy together with veliparib may kill more tumor cells.
PRIMARY OBJECTIVES: I. To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities of ABT-888 (veliparib) when combined with cisplatin and paclitaxel in women with advanced, persistent, or recurrent cervical cancer. II. To examine the safety of administering ABT-888 when combined with cisplatin and paclitaxel. III. Once the recommended phase II dose is established, to estimate the efficacy of cisplatin, paclitaxel, and ABT-888 with respect to objective tumor response in patients with advanced, persistent, or recurrent carcinoma of the cervix. SECONDARY OBJECTIVES: I. To examine the effects of this regimen on progression-free survival and overall survival. TERTIARY OBJECTIVES: I. To determine the proportion of patients with advanced, persistent, or recurrent cancer of the cervix whose tumors demonstrate loss of the Fanconi anemia group D2 (FancD2) foci formation. III. To determine the association between loss of FancD2 foci formation and progression-free survival, overall survival, and response in this patient population. OUTLINE: This is a phase I, dose-escalation study of veliparib followed by a phase II study. Patients receive paclitaxel intravenously (IV) over 3 hours on day 1, cisplatin IV over 1 hour on day 2, and veliparib orally (PO) on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
37
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 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
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Dose-limiting toxicities in the first course of treatment (Phase I)
Time frame: 21 days
Frequency and severity of adverse effects as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events v. 4.0
Time frame: Within 30 days of last protocol treatment
Objective tumor response (complete or partial response) (Phase II)
Time frame: Up to 5 years
Progression-free survival (Phase II)
Time frame: From study entry to time of progression or death, whichever occurs first, assessed up to 5 years
Overall survival (Phase II)
Time frame: From study entry to time of death or the date of last contact, assessed up to 5 years
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University of Mississippi Medical Center
Jackson, Mississippi, United States
Singing River Hospital
Pascagoula, Mississippi, United States
Washington University School of Medicine
St Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Case Western Reserve University
Cleveland, Ohio, United States
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