BRCA-Associated Breast Cancer

The study seeks to evaluate the efficacy and tolerability of veliparib/placebo in combination with carboplatin and paclitaxel in HER2-negative metastatic or locally advanced, unresectable, BRCA-associated breast cancer.

Veliparib

Veliparib

Capsule

40/Placebo, 50/Placebo, 100/Placebo, 50, 100

Primary Outcome Measures :
Progression free survival (PFS) [ Time Frame: Measured up to 3 years after the last subject has enrolled in the study. ]
Number of days from the date the subject is randomized to the date the subject experiences a confirmed event of disease progression or to the date of death if disease progression is not reached


Secondary Outcome Measures :
Overall survival (OS) [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
Number of days from the day the subject is randomized to the date of the subject's death

Clinical benefit rate (CBR) [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
Progression-free rate at 24 weeks from the Kaplan-Meier curve for time to progression

Objective response rate (ORR) [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
Proportion of subjects with a complete or partial objective response

Progression-free survival 2 (PFS2) [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
Days from randomization to the second objective radiographic progression or death of any cause after the first objective radiographic progression, whichever occurs first

Inclusion Criteria:

Histologically or cytologically confirmed breast cancer that is either locally advanced or metastatic. Locally advanced breast cancer must not be amenable to surgical resection or radiation with curative intent.
Suspected deleterious or deleterious BRCA1 and/or BRCA2 germline mutation.
Breast cancer must be HER2-negative.
Measurable or non-measurable (but radiologically evaluable) disease per Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1 on computed tomography (CT) scan (within 28 days of randomization) with at least one lesion outside previously irradiated areas.
Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2.
Adequate hematologic, renal, and hepatic function (within 28 days of randomization).

Exclusion Criteria:

1. More than two prior lines of cytotoxic chemotherapy (e.g., gemcitabine, doxorubicin, capecitabine) for metastatic disease.
- Regimens received in the adjuvant/neoadjuvant setting or for locally advanced breast cancer within the past 6 months will also be considered toward the maximum of 2 prior lines of therapy. Adjuvant/neoadjuvant chemotherapy for one cancer event will count as one prior line of therapy, if received within the past 6 months.
- Previous treatments with hormonal therapy (tamoxifen, aromatase inhibitors) and signal transduction agents (e.g., erlotinib, gefitinib, everolimus, bevacizumab) are allowed and are not counted towards the prior line of therapy.

2. Progressed or recurred within 12 months of completing platinum therapy or received > 1 prior line of platinum therapy for breast cancer in any setting (adjuvant, neoadjuvant, or metastatic).

3. Prior therapy with PARP inhibitors.

4. Prior taxane therapy administered for the treatment of metastatic breast cancer with the below exceptions.
- Prior taxane therapy for metastatic breast cancer is allowed if the patient received ≤ 1 full cycle (i.e., therapy discontinued within 4 weeks for subjects receiving weekly paclitaxel or Abraxane; therapy discontinued within 3 weeks for subjects receiving paclitaxel or docetaxel every 3 weeks) in the absence of progression or if taxane therapy for metastatic disease was > 12 months prior to C1D-2.
- Use of taxanes as adjuvant therapy or to treat locally advanced disease is permitted, if given more than 6 months prior to C1D-2

5. Known history of allergic reaction to cremophor-paclitaxel, carboplatin, Azo-Colourant Tartrazine (also known as FD&C Yellow 5 or E102), Azo-Colourant Orange Yellow-S (also known as FD&C Yellow 6 or E110) or known contraindications to any study supplied drug.

6. Active CNS metastases or leptomeningeal disease.