A Study Evaluating Talazoparib (BMN 673), a PARP Inhibitor, in Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (EMBRACA Study)
Condition: Breast Neoplasms; BRCA 1 Gene Mutation; BRCA 2 Gene Mutation
MeSH terms: Breast Neoplasms
Intervention: talazoparib; Physician's-Choice
Intervention description: Until progression or unacceptable toxicity develops; Capecitabine, Eribulin, Gemcitabine or Vinorelbine
Intervention MeSH terms: Talazoparib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 431.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast cancer; BRCA mutation; PARP inhibitor; BRCA 1; BRCA 2

Summary:

      The purpose of this open-label, 2:1 randomized phase III trial is to compare the safety and
      efficacy of talazoparib (also known as BMN 673) versus protocol-specific physician's choice
      in patients who have locally advanced and/or metastatic breast cancer with germline BRCA
      mutations.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed carcinoma of the breast

          -  Locally advanced breast cancer that is not amenable to curative radiation or surgical
             cure and/or metastatic disease appropriate for systemic single cytotoxic chemotherapy

          -  Documentation of a deleterious, suspected deleterious, or pathogenic germline BRCA1 or
             BRCA2 mutation from Myriad Genetics or other laboratory approved by the Sponsor

          -  No more than 3 prior chemotherapy-inclusive regimens for locally advanced and/or
             metastatic disease (no limit on prior hormonal therapies or targeted anticancer
             therapies such as mechanistic target of rapamycin (mTOR) or CDK4/6 inhibitors,
             immune-oncology agents, tyrosine kinase inhibitors, or monoclonal antibodies against
             CTL4 or VEGF)

          -  Prior treatment with a taxane and/or anthracycline in the neoadjuvant, adjuvant,
             locally advanced, or metastatic setting unless medically contraindicated

          -  Have measurable or non-measurable, evaluable disease by the revised response
             evaluation criteria in solid tumors (RECIST) v.1.1

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

        Exclusion Criteria:

          -  First-line locally advanced and/or metastatic breast cancer with no prior adjuvant
             chemotherapy unless the Investigator determines that one of the 4 cytotoxic
             chemotherapy agents in the control arm would otherwise be offered to the subject

          -  Prior treatment with a PARP inhibitor (not including iniparib)

          -  Not a candidate for treatment with at least 1 of the treatments of protocol-specific
             physician's choice (ie, capecitabine, eribulin, gemcitabine, vinorelbine)

          -  Subjects who had objective disease progression while receiving platinum chemotherapy
             administered for locally advanced or metastatic disease; subjects who received
             low-dose platinum therapy administered in combination with radiation therapy are not
             excluded

          -  Subjects who have received platinum in the adjuvant or neoadjuvant setting are
             eligible; however, subjects may not have relapsed within 6 months of the last dose of
             prior platinum therapy

          -  Cytotoxic chemotherapy within 14 days before randomization

          -  Radiation or anti-hormonal therapy or other targeted anticancer therapy within 14 days
             before randomization

          -  HER2 positive breast cancer

          -  Active inflammatory breast cancer

          -  CNS metastases

               -  Exception: Adequately treated brain metastases documented by baseline CT or MRI
                  scan that has not progressed since previous scans and that does not require
                  corticosteroids (except prednisone ≤ 5 mg/day or equivalent) for management of
                  CNS symptoms. A repeat CT or MRI following the identification of CNS metastases
                  (obtained at least 2 weeks after definitive therapy) must document adequately
                  treated brain metastases.

               -  Subjects with leptomeningeal carcinomatosis are not permitted

          -  Prior malignancy except for any of the following:

               -  Prior BRCA-associated cancer as long as there is no current evidence of the
                  cancer

               -  Carcinoma in situ or non-melanoma skin cancer

               -  A cancer diagnosed and definitively treated ≥ 5 years before randomization with
                  no subsequent evidence of recurrence

          -  Known to be human immunodeficiency virus positive

          -  Known active hepatitis C virus, or known active hepatitis B virus

          -  Known hypersensitivity to any of the components of talazoparib