This phase I trial studies the side effects and the best dose of veliparib when given together with paclitaxel and carboplatin in treating patients with solid tumors that are metastatic or cannot be removed by surgery and liver or kidney dysfunction. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, 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. Giving veliparib together with paclitaxel and carboplatin may kill more tumor cells.
PRIMARY OBJECTIVES: I. To determine the pharmacokinetics and pharmacodynamics of ABT-888 (veliparib) in patients with varying degrees of renal or hepatic dysfunction. II. To determine the maximum tolerated dose (MTD) of ABT-888 in combination with carboplatin and paclitaxel for patients with varying degrees of liver or kidney dysfunction. III. To provide dosing recommendations for ABT-888 in combination with carboplatin and paclitaxel based on degree of hepatic and renal impairment. SECONDARY OBJECTIVES: I. To define the dose-limiting toxicity (DLT) and other toxicities associated with the use of this combination in patients with varying degrees of renal or hepatic dysfunction. II. To evaluate the pharmacokinetic parameters of ABT-888, carboplatin, and paclitaxel when administered as a combination in patients with varying degrees of renal or hepatic dysfunction. III. To evaluate the pharmacodynamic measurement of poly-ADP-ribosylated (PAR) and platinum adducts in tumor cells associated with the use of this combination in patients with varying degrees of renal or hepatic dysfunction. OUTLINE: This is a dose-escalation study of veliparib. Patients receive veliparib\* orally (PO) twice daily (BID) on days 1-7 and paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 3. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. NOTE: \* All patients receive a single dose of veliparib PO on day -6 before course 1 (except patients with very severe renal dysfunction who receive veliparib on day -5 or -6 to coincide with a dialysis day). After completion of study treatment, patients are followed up for 4 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
94
Given IV
Correlative studies
Given IV
Correlative studies
Given PO
City of Hope Comprehensive Cancer Center
Duarte, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
City of Hope South Pasadena
South Pasadena, California, United States
Moffitt Cancer Center
Tampa, Florida, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
...and 7 more locations
PK parameters of veliparib
Standard quantitative and graphical statistical summaries of the derived PK parameters (e.g. area under curve and clearance) will be produced for each organ function cohort. The effect of dysfunction on pharmacokinetics will be explored by comparing each pharmacokinetic parameter across all cohorts using one-way analysis (analysis of variance) or Kruskal-Wallis test. The level of each protein will be compared between responders and non-responders using the Wilcoxon signed rank test.
Time frame: Day -6 and 3 of course 1 after veliparib dosing
MTD of veliparib in combination with carboplatin and paclitaxel, determined according to incidence of DLT as graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.0
Time frame: 21 days
Incidence of toxicities as assessed by NCI CTCAE v4.0
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, grade and dose level. Severe and life-threatening toxicities and adverse event-related deaths (\>= grade 3) will be described on a patient-by-patient basis and will include any relevant baseline data.
Time frame: Up to 4 weeks after completion of study treatment
Response rate as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Responses will be tabulated by disease diagnosis and by dose level. 95% confidence limits will also be reported on the response rates.
Time frame: Up to 4 weeks after completion of study treatment
Incidence of stable disease as assessed by RECIST version 1.1
Incidence of stable disease will be tabulated by disease diagnosis and by dose level.
Time frame: Up to 4 weeks after completion of study treatment
Time to progression
Displayed for all patients and for patients who have responded; no formal statistical analysis is planned.
Time frame: Up to 4 weeks after completion of study treatment
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