A Phase III Trial of Niraparib Versus Physician's Choice in Her2 Negative, Germline BRCA Mutation-positive Breast Cancer Patients (BRAVO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Tesaro, Inc.
Sponsor:
Collaborators:
European Organisation for Research and Treatment of Cancer - EORTC
Breast International Group
Myriad Genetic Laboratories, Inc.
US Oncology Research
Sarah Cannon
Facing Our Risk of Cancer Empowered (FORCE)
Information provided by (Responsible Party):
Tesaro, Inc.
ClinicalTrials.gov Identifier:
NCT01905592
First received: July 18, 2013
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to compare progression-free survival (PFS)in patients with advanced/metastatic breast cancer who have a BRCA gene change when treated with niraparib as compared to those treated with physician's choice


Condition Intervention Phase
Carcinoma of Breast
Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
BRCA1 Gene Mutation
BRCA2 Gene Mutation
Drug: niraparib
Drug: Physician's choice
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Open Label, Multicenter, Controlled Trial of Niraparib Versus Physician's Choice in Previously-treated, Her2 Negative, Germline BRCA Mutation-positive Breast Cancer Patients

Resource links provided by NLM:


Further study details as provided by Tesaro, Inc.:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: After 96 PFS events (40%) have been documented. Anticipated in about 16 months from first patient enrolled ] [ Designated as safety issue: No ]
    The primary objective of this study is to compare progression-free survival as determined by central, blinded review, of patients with advanced/metastatic HER2-negative breast cancer who have a gBRCAmut when treated with niraparib as compared to those treated with physician's choice


Secondary Outcome Measures:
  • Overall survival [ Time Frame: 54 months after the first patient is enrolled ] [ Designated as safety issue: No ]
    To compare overall survival of patients with advanced/metastatic HER2-negative breast cancer who have a gBRCAmut when treated with niraparib as compared to those treated with physician's choice


Other Outcome Measures:
  • Health related quality of life [ Time Frame: End of study Oct 2015 ] [ Designated as safety issue: No ]
    2 validated questionnaires to assess general quality of life and deterioration due to breast cancer


Estimated Enrollment: 306
Study Start Date: October 2013
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Physician's choice
Physician may select from 4 active comparators
Drug: Physician's choice
Choice of 4 standard of care metastatic breast cancer chemotherapies
Experimental: niraparib
Patients will be randomized 2:1 to receive niraparib 3 oral capsules (100mg) once daily for 21 continuous days
Drug: niraparib
Until progression or unacceptable toxicity develops
Other Name: formerly MK-4827

Detailed Description:

This is a phase III, randomized, open label, multicenter, controlled trial of niraparib versus physician's choice in previously-treated, HER2 negative, germline BRCA mutation-positive breast cancer patients. Niraparib is an orally active parp inhibitor. Niraparib (in a 2:1 ratio) will be administered once daily continuously during a 21-day cycle. Physician's choice will be administered on a 21-day cycle. Health-related quality of life will be measured. The Safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), and safety laboratory values.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Germline BRCA1 or BRCA2 mutation; patients with unknown BRCA status who meet NCCN BRCA screening criteria will be screened for BRCA mutation.
  2. Metastatic or locally advanced disease that is not amenable to resection or radiation with curative intent.
  3. Up to 2 prior cytotoxic regimens for advanced or metastatic breast cancer patients with no prior cytotoxic regimens for advanced or metastatic disease will only be allowed if they relapsed during or within 12 months of (neo-) adjuvant cytotoxic therapy that included a taxane and anthracycline, if not contraindicated.
  4. Prior therapy should have included an anthracycline and a taxane (or contraindication to those) in the neoadjuvant, adjuvant, or advanced/metastatic setting.

    a. Hormone receptor positive patients must also have hormone resistant disease (progression during at least one prior hormonal therapy) for which chemotherapy is indicated.

  5. ECOG performance status 0-2
  6. Adequate bone marrow, kidney and liver function

Exclusion Criteria:

  1. Patients with platinum resistant cancer
  2. Symptomatic uncontrolled brain metastasis
  3. Prior diagnosis of Stage IV ovarian cancer; Stage III ovarian cancer must have a 5-year disease-free interval and normal CA125; Stage II ovarian cancer must have a 2-year disease-free interval and normal CA125
  4. Known hypersensitivity to the components of niraparib
  5. Invasive cancer other than ovarian cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated)
  6. Symptomatic uncontrolled brain metastasis
  7. Pregnant or breast feeding patients
  8. Immunocompromised patients
  9. Known active Hepatitis B or C
  10. Prior treatment with a PARP inhibitor
  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: NCT01905592

Contacts
Contact: Shefali Agarwal, MD 781-916-8375 sagarwal@tesarobio.com

  Show 36 Study Locations
Sponsors and Collaborators
Tesaro, Inc.
European Organisation for Research and Treatment of Cancer - EORTC
Breast International Group
Myriad Genetic Laboratories, Inc.
US Oncology Research
Sarah Cannon
Facing Our Risk of Cancer Empowered (FORCE)
Investigators
Study Chair: Nicholas Turner, MD Breast International Group
Study Chair: Judith Balmana, MD Hospital Universitari Vall d'Hebron
Principal Investigator: David Cameron, MD European Organisation for Research and Treatment of Cancer
Principal Investigator: William Audeh, MD Cedars-Sinai Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Tesaro, Inc.
ClinicalTrials.gov Identifier: NCT01905592     History of Changes
Other Study ID Numbers: PR-30-5010-C, 1307-BCG, BIG5-13
Study First Received: July 18, 2013
Last Updated: July 24, 2014
Health Authority: United States: Food and Drug Administration
EU: EMEA

Keywords provided by Tesaro, Inc.:
Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
BRCA1 Gene Mutation
BRCA2 Gene Mutation
Parp Inhibitor
BRCA

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on July 24, 2014