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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Medivation, Inc.
Sponsor:
Information provided by (Responsible Party):
Medivation, Inc.
ClinicalTrials.gov Identifier:
NCT01945775
First received: September 11, 2013
Last updated: August 16, 2016
Last verified: August 2016
  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.

Condition Intervention Phase
Breast Neoplasms
BRCA 1 Gene Mutation
BRCA 2 Gene Mutation
Drug: talazoparib
Drug: Physician's-Choice
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Medivation, Inc.:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Anticipated in about 41 months following first patient enrolled ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate objective response rate (ORR) [ Time Frame: Anticipated in about 41 months following first patient enrolled ] [ Designated as safety issue: No ]
  • Evaluate overall survival (OS) [ Time Frame: Anticipated in about 41 months following first patient enrolled ] [ Designated as safety issue: No ]
  • Safety as assessed by percentage of patients with any Adverse Event (AE) [ Time Frame: Anticipated in about 41 months following first patient enrolled ] [ Designated as safety issue: No ]
  • Pharmacokinetics of talazoparib as assessed by trough plasma concentrations [ Time Frame: Anticipated in about 41 months following first patient enrolled ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Duration of response (DOR) for objective responders [ Time Frame: Anticipated in about 41 months following first patient enrolled ] [ Designated as safety issue: No ]
  • Health-related quality of life [ Time Frame: Anticipated in about 41 months following first patient enrolled ] [ Designated as safety issue: No ]
    2 Validated questionnaires to assess general quality of life and deterioration due to breast cancer


Estimated Enrollment: 429
Study Start Date: October 2013
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: talazoparib
Patient will be randomized 2:1 to receive talazoparib oral capsules (1.0 mg) once daily for 21 continuous days
Drug: talazoparib
Until progression or unacceptable toxicity develops
Active Comparator: Physician's-Choice
Capecitabine, Eribulin, Gemcitabine or Vinorelbine
Drug: Physician's-Choice
Capecitabine, Eribulin, Gemcitabine or Vinorelbine

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01945775

Contacts
Contact: Medivation Clinical Operations +1 (415) 543-3470 dg-embraca@medivation.com
Contact: Medivation Clinical Trial Disclosure TrialDisclosure@Medivation.com

  Show 208 Study Locations
Sponsors and Collaborators
Medivation, Inc.
  More Information

Responsible Party: Medivation, Inc.
ClinicalTrials.gov Identifier: NCT01945775     History of Changes
Other Study ID Numbers: 673-301  U1111-1155-7579 
Study First Received: September 11, 2013
Last Updated: August 16, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Medivation, Inc.:
Breast cancer
BRCA mutation
PARP inhibitor
BRCA 1
BRCA 2

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Poly(ADP-ribose) Polymerase Inhibitors
Talazoparib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 24, 2016