PARP Inhibition for Triple Negative Breast Cancer (ER-/PR-/HER2-)With BRCA1/2 Mutations

The purpose of this trial is to evaluate 2-year disease-free survival in this patient population treated with single agent cisplatin and patients treated with cisplatin in combination with Rucaparib following preoperative chemotherapy. Side effects and tolerability of this treatment in patients with residual disease following preoperative chemotherapy will also be observed and characterized.

OUTLINE: This is a multi-center study. Safety Run-in will be for the first 12 patients on study only (6 in cohort 1 and 6 in cohort 2). Patients in the safety run will be included in the efficacy analysis on intent to treat basis: Cisplatin 75 mg/m2 IV D1 every 3 weeks x 4 cycles; Rucaparib 16-30 mg IV D 1,2,3 every 3 weeks x 4 cycles If cycle 1 is well tolerated, the dose of Rucaparib will be escalated from 16 mg to 24 mg for subsequent cycles in the cohort 1, and 24 mg to 30 mg in the cohort 2. If ≤ 1 of 6 patients in cohort 1 experiences DLT, cohort 2 will commence. If 2 or more of 6 patients in cohort 1 experience DLT, the study will be suspended and an amendment to explore lower doses will be considered. If ≤ 1 of 6 patients in cohort 2 experiences DLT, the randomized portion of the study will commence. If 2 or more of 6 patients experience DLT, the study will be suspended and an amendment to proceed with the randomized portion at the cohort 2 dose (24 mg) will be considered. During the randomized portion of the study, patients will be randomized to either Arm A or Arm B. Stratification factors: * Anthracycline vs. not * Residual LN involvement vs. No Residual LN involvement Arm A (Cisplatin Monotherapy) Cisplatin 75 mg/m2 IV D1 every 3 weeks x 4 cycles Arm B (Combination Therapy) Cisplatin 75 mg/m2 IV D1 every 3 weeks x 4 cycles; Rucaparib 16-30 mg IV D1,2,3 every 3 weeks x 4 cycles Rucaparib maintenance 30 mg IV weekly x 24 weeks ECOG Performance Status 0-1 Life Expectancy: Not Specified Hematopoietic: * Hemoglobin (Hgb) \> 9.0 g/dL * Platelets \> 100 K/ mm3 * Absolute neutrophil count (ANC) \> 1.5 K/mm3 Hepatic: * Bilirubin \< upper limit of normal (except in patients with documented Gilbert's disease, who must have a total bilirubin \< 3.0 mg/dL) * Aspartate aminotransferase (AST, SGOT) \< 2.5 x ULN * Alanine aminotransferase (ALT, SGPT) \< 2.5 x ULN Renal: * Calculated creatinine clearance of \> 50 cc/min using the Cockcroft-Gault formula Cardiovascular: * Left ventricular ejection fraction within normal limits. * Patients with an unstable angina or myocardial infarction within 12 months of study entry are excluded. * No clinically significant arrhythmia or baseline ECG abnormalities in the opinion of the treating investigator.