Veliparib With or Without Carboplatin in Treating Patients With Stage III or Stage IV Breast Cancer

• Response rate as measured by RECIST version 1.1 [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  

• Progression-free survival [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 4 years ] [ Designated as safety issue: No ]
  Compared between arms using the log-rank test. Analyzed using Kaplan-Meier plots and multivariate Cox regression.
  
  
• Toxicity graded according to the NCI CTCAE version 4.0 [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
  Assessed and summarized with descriptive statistics.
  
  

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of single agent ABT-888 (veliparib) (NSC 737664) in BRCA carriers with metastatic breast cancer based on response rate (RECIST criteria).

SECONDARY OBJECTIVES:

I. To conduct subset analysis on BRCA1 vs. BRCA2 and hormone receptor status. II. To evaluate progression-free survival of patients on single-agent ABT-888. III. To further describe the safety and tolerability of ABT-888 (NSC 737664) as a single agent and in combination with carboplatin for BRCA-associated breast cancer.

IV. To evaluate the pharmacokinetics of ABT-888 (NSC 737664) alone and in combination with carboplatin.

V. To assess the relationship between the level of PARP inhibition by ABT-888 and biomarkers of DNA damage in PBMC's and in tumor VI. To explore the relationship between biomarkers of drug effect and progression-free survival.

VII. To evaluate the efficacy and safety of the combination of carboplatin and ABT-888 in patients who have failed single agent ABT-888.

VIII. To conduct subset analysis on BRCA1 vs. BRCA2 and hormone receptor status.

OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status (0-1 vs 2), and hormone status (estrogen receptor [ER]- and/or progesterone receptor [PR]-positive vs ER- and/or PR-negative). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral veliparib twice daily on days 1-21.

ARM II: Patients receive carboplatin IV over 30 minutes on day 1 and veliparib as in arm I.

In both arms, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood and hair follicle sample collection for pharmacokinetics and other laboratory studies.

After completion of study therapy, patients are followed up every 3-6 months.