A Phase 3 Randomized, Placebo-controlled Trial of Carboplatin and Paclitaxel With or Without Veliparib (ABT-888) in HER2-negative Metastatic or Locally Advanced Unresectable BRCA-associated Breast Cancer

The primary objective of the study is to assess the progression-free survival (PFS) of veliparib in combination with carboplatin and paclitaxel (C/P) compared to placebo plus C/P in participants with a Breast Cancer Gene 1 or 2 (BRCA1; BRCA2) mutation in Human Epidermal Growth Factor Receptor 2 (HER2)-negative metastatic or locally advanced unresectable breast cancer. The secondary objectives of the study are to assess overall survival (OS), clinical benefit rate (CBR) through the end of Week 24, objective response rate (ORR) and PFS on subsequent therapy (PFS2) in participants treated with veliparib in combination with C/P versus placebo in combination with C/P.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

1. 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.
2. Suspected deleterious or deleterious Breast Cancer Gene 1 (BRCA1) and/or Breast Cancer Gene 2 (BRCA2) germline mutation.
3. Breast cancer must be Human Epidermal Growth Factor Receptor 2 (HER2)-negative.
4. 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.
5. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2.
6. 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 Poly(ADP-ribose)-Polymerase (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 Cycle 1 Day-2 (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.

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