Clinical Trials /

A Study Evaluating Talazoparib (BMN 673), a PARP Inhibitor, in Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (EMBRACA Study)

NCT01945775

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title:A Study Evaluating Talazoparib (BMN 673), a PARP Inhibitor, in Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (EMBRACA Study)
  • Official Title:A Phase 3, Open-Label, Randomized, Parallel, 2-Arm, Multi-Center Study of Talazoparib (BMN 673) Versus Physician's Choice in Germline BRCA Mutation Subjects With Locally Advanced and/or Metastatic Breast Cancer, Who Have Received Prior Chemotherapy Regimens for Metastatic Disease

Clinical Trial IDs

  • ORG STUDY ID: 673-301
  • SECONDARY ID: U1111-1155-7579
  • NCT ID: NCT01945775

Trial Conditions

  • Breast Neoplasms
  • BRCA 1 Gene Mutation
  • BRCA 2 Gene Mutation

Trial Interventions

DrugSynonymsArms
talazoparibtalazoparib
Physician's-ChoicePhysician's-Choice

Trial Purpose

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.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
talazoparibExperimentalPatient will be randomized 2:1 to receive talazoparib oral capsules (1.0 mg) once daily for 21 continuous days
  • talazoparib
    Physician's-ChoiceActive ComparatorCapecitabine, Eribulin, Gemcitabine or Vinorelbine
      • Physician's-Choice

    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

    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Both
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Progression Free Survival (PFS)
    Time Frame:Anticipated in about 41 months following first patient enrolled
    Safety Issue:No
    Description:

    Secondary Outcome Measures

    Measure:Evaluate objective response rate (ORR)
    Time Frame:Anticipated in about 41 months following first patient enrolled
    Safety Issue:No
    Description:
    Measure:Evaluate overall survival (OS)
    Time Frame:Anticipated in about 41 months following first patient enrolled
    Safety Issue:No
    Description:
    Measure:Safety as assessed by percentage of patients with any Adverse Event (AE)
    Time Frame:Anticipated in about 41 months following first patient enrolled
    Safety Issue:No
    Description:
    Measure:Pharmacokinetics of talazoparib as assessed by trough plasma concentrations
    Time Frame:Anticipated in about 41 months following first patient enrolled
    Safety Issue:No
    Description:

    Trial Keywords

    • Breast cancer
    • BRCA mutation
    • PARP inhibitor
    • BRCA 1
    • BRCA 2