Study Evaluating Efficacy And Tolerability Of Veliparib in Combination With Temozolomide (TMZ) or In Combination With Carboplatin and Paclitaxel Versus Placebo in Participants With Breast Cancer Gene (BRCA)1 and BRCA2 Mutation and Metastatic Breast Cancer
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Placebo; Veliparib; Carboplatin; Temozolomide; Paclitaxel
Intervention MeSH terms: Paclitaxel; Carboplatin; Temozolomide; Veliparib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 294.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PARP; TMZ; Temodal; Carboplatin; veliparib; BRCA2 mutation carrier; Breast cancer; Metastatic breast cancer; temozolomide; BRCA1 mutation carrier; ABT-888; Paclitaxel; Recurrent breast cancer; Temodar; Locally recurrent

Summary:

      The primary objective of the study is to assess the progression-free survival (PFS) of oral
      veliparib in combination with TMZ or in combination with carboplatin and paclitaxel compared
      to placebo plus carboplatin and paclitaxel in subjects with BRCA1 or BRCA2 mutation and
      locally recurrent or metastatic breast cancer.
    

Eligibility criteria:

        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, active infection, myocardial infarction,
             stroke, or transient ischemic attack, psychiatric illness/social situations that would
             limit compliance.

          -  Pregnant or breastfeeding.