The Study Evaluating Efficacy And Tolerability Of Veliparib in Combination With Temozolomide or In Combination With Carboplatin and Paclitaxel Versus Placebo in Subjects With BRCA1 and BRCA2 Mutation and Metastatic Breast Cancer

• Overall Survival [ Time Frame: From Cycle 1 Day 1 until patient's death or 3 years post discontinuation ] [ Designated as safety issue: No ]
• Clinical Benefit Rate (CBR) [ Time Frame: From Cycle 1 Day1 until patient's death or 3 years post discontinuation ] [ Designated as safety issue: No ]
• Objective Response Rate [ Time Frame: From Cycle 1 Day 1 until patient's death or 3 years post discontinuation ] [ Designated as safety issue: No ]

• Overall Survival [ Time Frame: From Randomization until patient's death or 3 years post discontinuation ] [ Designated as safety issue: No ]
• Clinical Benefit Rate (CBR) [ Time Frame: From Randomization until patient's death or 3 years post discontinuation ] [ Designated as safety issue: No ]
• Objective Response Rate [ Time Frame: From Randomization until patient's death or 3 years post discontinuation ] [ Designated as safety issue: No ]

The Study Evaluating Efficacy And Tolerability of Veliparib in Combination with Temozolomide or Veliparib/Placebo in Combination with Carboplatin and Paclitaxel in Subjects with locally recurrent Breast Cancer not amenable to therapy with curative intent, or metastatic breast cancer and a documented (BRCA1) and (BRCA2) deleterious germline mutation.

Subjects will be randomized in a 1:1:1 ratio to one of the three treatment groups. The safety of each treatment group will be assessed by evaluating study drug exposure, adverse events, serious adverse events, all deaths, changes in laboratory determinations, and vital sign parameters. The Clinical Benefit Rate (CBR) and Objective Response Rate (ORR) as well as Progression-free survival (PFS) using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be assessed. Study visits will be conducted according to the protocol schedule and randomization group. Study visits will include physical examination, laboratory blood sample collection, and assessment of vital signs, medical history and urinalysis. 12-lead Electrocardiogram (ECG) will be performed at protocol specified visits.

• Drug: Veliparib
  Days 1 through 7 of 28-day cycle (in combination with Temozolomide) or Days 1 through 7 of 21-day cycle (in combination with Carboplatin and Paclitaxel).
  Other Name: ABT-888
• Drug: Temozolomide
  Days 1 through 5 of 28-day cycle (in combination with veliparib).
  Other Name: Temodal
• Drug: Carboplatin
  Day 3 of 21-day cycle
• Drug: Paclitaxel
  Day 3 of 21-day cycle.
  Other Name: Taxol
• Drug: Placebo
  Placebo comparator for Veliparib days 1 through 7 of 21-day cycle (in combination with carboplatin and/or paclitaxel).

• Experimental: Veliparib with Temozolomide
  Veliparib on Day 1 thru 7 and temozolomide on Day 1 thru 5 of a 28-day cycle.
  Interventions:

  • Drug: Veliparib
  • Drug: Temozolomide
• Experimental: Veliparib with Carboplatin and Paclitaxel
  Veliparib on Day 1 thru 7 and carboplatin/paclitaxel on Day 3 of a 21-day cycle.
  Interventions:

  • Drug: Veliparib
  • Drug: Carboplatin
  • Drug: Paclitaxel
• Placebo Comparator: Placebo with Carboplatin and Paclitaxel
  Placebo on Day 1 thru 7 and carboplatin/paclitaxel on Day 3 of a 21-day cycle.
  Interventions:

  • Drug: Carboplatin
  • Drug: Paclitaxel
  • Drug: Placebo

Inclusion Criteria:

• Histologically or cytologically confirmed breast cancer that is either locally recurrent or metastatic.
• Locally recurrent disease must not be amenable to surgical resection or radiation with curative intent.
• Must have a documented deleterious Breast Cancer Gene BRCA1 or BRCA2 germline mutation.
• If Human Epidermal Growth Factor Receptor (HER2) positive, subjects must have received and progressed on at least one prior standard HER2 directed therapy or the subject must be ineligible to receive anti-HER2 therapy.
• Measurable or non-measurable (but radiologically evaluable) disease by RECIST (Response Evaluation Criteria in Solid Tumors) criteria 1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.
• Subject must have adequate bone marrow, renal and hepatic function.
• Subject must not be pregnant or plan to conceive a child.

Exclusion Criteria:

• Received anticancer agent(s) or an investigational agent within 21 days prior to C1D1, or radiotherapy within 28 days prior Cycle 1 Day 1
• More than 2 prior lines of cytotoxic chemotherapy
• Prior treatment of breast cancer with temozolomide, a platinum agent, or a Poly (ADP ribose) Polymerase (PARP) inhibitor.
• Prior taxane therapy for metastatic breast cancer.
• A history of or evidence of brain metastases or leptomeningeal disease.
• A history of uncontrolled seizure disorder
• Pre-existing neuropathy from any cause in excess of Grade 1
• Known history of allergic reaction to cremophor/paclitaxel
• Clinical significant uncontrolled conditions â€" active infection, myocardial infarction, stroke, or transient ischemic attack, psychiatric illness/social situations that would limit compliance.
• Pregnant or breastfeeding