Clinical Trial 17835

Cancer Type: Breast
Interventions:Not Applicable; Paraplatin (carboplatin); Placebo; Taxol (paclitaxel); Veliparib (ABT-888); carboplatin; paclitaxel

Study Type: Treatment
Phase of Study: Phase III


    Study Title

    A Phase 3 Randomized, Placebo-Controlled Trial of Carboplatin and Paclitaxel With or Without the PARP Inhibitor Veliparib (ABT-888) in HER2-Negative Metastatic or Locally Advanced Unresectable BRCA-Associated Breast Cancer


    The main purpose of the study is to determine if veliparib in combination with carboplatin and paclitaxel improves the efficacy of chemotherapy alone in participants with a BRCA1 or BRCA2 mutation and HER2-negative metastatic or locally advanced breast cancer.


    The primary endpoint is to assess the progression-free survival (PFS) of veliparib in combination with carboplatin (C) and paclitaxel (P) compared to placebo with C/P in subjects with a BRCA1 and/or BRCA2 Mutation and 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), objective response rate (ORR), PFS2 and duration of overall response (DOR) in subjects treated with veliparib in combination with C/P versus subjects treated with placebo with C/P. The tertiary objectives are to assess change in ECOG performance status, change in Quality of Life (QoL).

    Inclusion Criteria

  • Histologically or cytologically confirmed breast cancer that is either locally advanced or metastatic. Locally advanced breast cancer must not be primarily amenable to surgical resection or radiation with curative intent. Participants with bone-only disease and/or hormone receptor positive disease should be deemed by the investigator as appropriate candidates for combination chemotherapy.
  • Suspected deleterious or deleterious BRCA1 and/or BRCA2 germline mutation. Potential participants with BRCA variants of uncertain significance or polymorphisms in BRCA1 or BRCA2 will not be eligible for the study.
  • 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

  • Received anticancer agent(s) or an investigational agent within 21 days prior to C1D-2 or radiotherapy within 28 days prior to C1D-2. Prior treatment with palliative local breast or bone lesion radiation (other than pelvis) can occur, if administered at least 14 days prior to C1D-2. Anticancer hormonal therapy must be stopped 7 days before starting C1D-2.
  • Received 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.
  • 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).
  • Prior therapy with PARP inhibitors.
  • Prior taxane therapy administered for the treatment of metastatic breast cancer with the following exceptions: A) Prior taxane therapy for metastatic breast cancer is allowed if the patient received ≤ 1 full cycle (i.e., therapy discontinued within 4 weeks for participants receiving weekly paclitaxel or Abraxane; therapy discontinued within 3 weeks for participants 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. B) Use of taxanes as adjuvant therapy or to treat locally advanced disease is permitted, if given more than 6 months prior to C1D-2.
  • 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.
  • Active central nervous system (CNS) metastases or leptomeningeal disease.