A Study Evaluating Safety and Efficacy of the Addition of ABT-888 Plus Carboplatin Versus the Addition of Carboplatin to Standard Chemotherapy Versus Standard Chemotherapy in Subjects With Early Stage Triple Negative Breast Cancer

• Rate of eligibility for breast conservation after therapy (BCR). [ Time Frame: At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug). ]
  Whether a subject is eligible for breast conserving surgery will be determined by the subject's surgeon prior to chemotherapy and after completion of chemotherapy.
• Event Free Survival (EFS) [ Time Frame: Up to 10 years from first dose of study drug. ]
  EFS will be defined as the time from random assignment to documentation of the first of the following events: failure to reach potential curative surgery; local, regional, or distant invasive recurrence of breast cancer following curative surgery; a contralateral breast cancer; a new onset malignancy; or death as a result of any cause.
• Overall Survival (OS) [ Time Frame: Up to 10 years from first dose of study drug. ]
  OS will be defined as the number of days from the day the subject is randomized to the date of the subject's death.

• Clinical Response Rate (CRR) [ Time Frame: First day of treatment on Chemotherapy Segment 2 (approximately 12-16 weeks from first dose of study drug). ]
  CRR at 12 weeks and tumor sizes at 12 weeks will be summarized at the end of the Chemotherapy Segment 1 of the treatment (reported at visit AC1) to assess the objective response rate. CRR is defined as the proportion of subjects with complete or partial response of the primary tumor as determined by the central imaging vendor.
• pCR plus minimal residual disease (defined as residual cancer burden [RCB] class I) [ Time Frame: At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug). ]
  RCB in the breast tissue and the lymph node tissue will be assessed upon completion of pre-operative systemic therapy and definitive surgery.
• Eastern Cooperative Oncology Group (ECOG) performance status. [ Time Frame: First day of treatment (Day 1) to Pre-Op Visit (approximately 22-32 weeks from first dose of study drug). ]
  ECOG performance status will be determined by the Investigator at each assessment.
• Breast cancer related quality of life (QoL). [ Time Frame: First day of treatment (Day 1) up to 6 months during the post-surgery follow-up period (approximately 15 months from first dose of study drug). ]
  Breast cancer related QoL will be assessed via the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), Breast Cancer module (EORTC QLQ-BR23) and European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L) questionnaires.

• Event Free Survival (EFS) [ Time Frame: Up to 10 years from first dose of study drug. ]
  EFS will be defined as the time from random assignment to documentation of the first of the following events: failure to reach potential curative surgery; local, regional, or distant invasive recurrence of breast cancer following curative surgery; a contralateral breast cancer; a new onset malignancy; or death as a result of any cause.
• Overall Survival (OS) [ Time Frame: Up to 10 years from first dose of study drug. ]
  OS will be defined as the number of days from the day the subject is randomized to the date of the subject's death.
• Clinical Response Rate (CRR) [ Time Frame: First day of treatment on Chemotherapy Segment 2 (approximately 12-16 weeks from first dose of study drug). ]
  CRR at 12 weeks and tumor sizes at 12 weeks will be summarized at the end of the Chemotherapy Segment 1 of the treatment (reported at visit AC1) to assess the objective response rate. CRR is defined as the proportion of subjects with complete or partial response of the primary tumor as determined by the central imaging vendor.
• pCR plus minimal residual disease (defined as residual cancer burden [RCB] class I) [ Time Frame: At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug). ]
  RCB in the breast tissue and the lymph node tissue will be assessed upon completion of pre-operative systemic therapy and definitive surgery.
• Eastern Cooperative Oncology Group (ECOG) performance status. [ Time Frame: First day of treatment (Day 1) to Pre-Op Visit (approximately 22-32 weeks from first dose of study drug). ]
  ECOG performance status will be determined by the Investigator at each assessment.
• Breast cancer related quality of life (QoL). [ Time Frame: First day of treatment (Day 1) up to 6 months during the post-surgery follow-up period (approximately 15 months from first dose of study drug). ]
  Breast cancer related QoL will be assessed via the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), Breast Cancer module (EORTC QLQ-BR23) and European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L) questionnaires.

• Drug: Veliparib
  Veliparib
• Drug: Carboplatin
  Carboplatin
• Drug: Paclitaxel
  Paclitaxel
• Drug: Doxorubicin
  Doxorubicin
• Drug: Cyclophosphamide
  Cyclophosphamide
• Drug: Placebo
  Placebo for Veliparib
• Drug: Placebo
  Placebo for Carboplatin

• Active Comparator: Arm A
  Veliparib + carboplatin + paclitaxel followed by doxorubicin/cyclophosphamide (AC)
  Interventions:

  • Drug: Veliparib
  • Drug: Carboplatin
  • Drug: Paclitaxel
  • Drug: Doxorubicin
  • Drug: Cyclophosphamide
• Placebo Comparator: Arm B
  Placebo + carboplatin + paclitaxel followed by AC
  Interventions:

  • Drug: Carboplatin
  • Drug: Paclitaxel
  • Drug: Doxorubicin
  • Drug: Cyclophosphamide
  • Drug: Placebo
• Placebo Comparator: Arm C
  Placebo + placebo + paclitaxel followed by AC.
  Interventions:

  • Drug: Paclitaxel
  • Drug: Doxorubicin
  • Drug: Cyclophosphamide
  • Drug: Placebo
  • Drug: Placebo

Inclusion Criteria:

1. Histologically confirmed invasive breast cancer by core needle or incisional biopsy (excisional biopsy is not allowed). Tumors must be clinical stage T2-3 N0-2 or T1 N1-2 per AJCC Staging Edition 7 or clinical stage T2-3 N0-2 or T1 N1-2 by physical exam or radiologic studies.
2. Documented Breast Cancer Gene (BRCA) germline mutation testing.
3. Estrogen Receptor (ER)-, Progesterone Receptor (PR)-, and Human Epidermal Growth Factor Receptor (HER)2-negative (triple-negative) cancer of the breast.
4. ECOG Performance status of 0 to 1.
5. Women must be determined to be not of childbearing potential (surgically sterile, or postmenopausal defined as amenorrheic for at least 12 months) by the Investigator OR they must have a negative serum pregnancy test prior to randomization.

Exclusion Criteria:

1. Previous anti-cancer treatment (cytotoxic chemotherapy, immunotherapy, biologic therapy radiotherapy or investigational agents) with therapeutic intent for current breast cancer.
2. Previous treatment with carboplatin, paclitaxel, doxorubicin, cyclophosphamide and a Poly-(ADP-ribose)-Polymerase (PARP) inhibitor.
3. Concurrent treatment with an ovarian hormonal replacement therapy or with hormonal agents such as raloxifene, tamoxifen or other selective estrogen receptor modulator (SERM). Subjects must have discontinued use of such agents prior to beginning study treatment.
4. A history of seizure within 12 months prior to study entry.
5. Pre-existing neuropathy from any cause in excess of Grade 1.

• US Oncology Research
• NSABP Foundation Inc
• Alliance for Clinical Trials in Oncology
• German Breast Group
• Grupo Español de Investigación del Cáncer de Mama