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A Phase III Trial of Niraparib Versus Physician's Choice in HER2 Negative, Germline BRCA Mutation-positive Breast Cancer Patients (BRAVO)

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ClinicalTrials.gov Identifier: NCT01905592
Recruitment Status : Active, not recruiting
First Posted : July 23, 2013
Last Update Posted : November 6, 2017
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
Information provided by (Responsible Party):
Tesaro, Inc.

Tracking Information
First Submitted Date  ICMJE July 18, 2013
First Posted Date  ICMJE July 23, 2013
Last Update Posted Date November 6, 2017
Study Start Date  ICMJE October 2013
Estimated Primary Completion Date May 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 18, 2014)
Progression Free Survival (PFS) [ Time Frame: December 2015 ]
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
Original Primary Outcome Measures  ICMJE
 (submitted: July 18, 2013)
Progression Free Survival (PFS) [ Time Frame: After 96 PFS events (40%) have been documented. Anticipated in about 16 months from first patient enrolled ]
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
Change History Complete list of historical versions of study NCT01905592 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2014)
Overall survival [ Time Frame: March 2016 ]
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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2013)
Overall survival [ Time Frame: 54 months after the first patient is enrolled ]
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
Current Other Pre-specified Outcome Measures
 (submitted: September 18, 2014)
Health related quality of life [ Time Frame: End of study ]
2 validated questionnaires to assess general quality of life and deterioration due to breast cancer
Original Other Pre-specified Outcome Measures
 (submitted: July 18, 2013)
Health related quality of life [ Time Frame: End of study Oct 2015 ]
2 validated questionnaires to assess general quality of life and deterioration due to breast cancer
 
Descriptive Information
Brief Title  ICMJE A Phase III Trial of Niraparib Versus Physician's Choice in HER2 Negative, Germline BRCA Mutation-positive Breast Cancer Patients
Official Title  ICMJE 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
Brief Summary 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Carcinoma of Breast
  • Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
  • BRCA1 Gene Mutation
  • BRCA2 Gene Mutation
Intervention  ICMJE
  • Drug: niraparib
    Until progression or unacceptable toxicity develops
    Other Name: formerly MK-4827
  • Drug: Physician's choice
    Choice of 4 standard of care metastatic breast cancer chemotherapies
Study Arms  ICMJE
  • Active Comparator: Physician's choice
    Physician may select from 4 active comparators
    Intervention: Drug: Physician's choice
  • Experimental: niraparib
    Patients will be randomized 2:1 to receive niraparib 3 oral capsules (100mg) once daily for 21 continuous days
    Intervention: Drug: niraparib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: July 18, 2013)
306
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2018
Estimated Primary Completion Date May 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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/or anthracycline, if not contraindicated.
  4. Prior therapy should have included a taxane and/or anthracycline (unless 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 metastases
  3. Prior diagnosis of Stage IV ovarian cancer; Stage III ovarian cancer must have a 5-year disease-free interval; Stage II ovarian cancer must have a 2-year disease-free interval
  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. Pregnant or breast feeding patients
  7. Immunocompromised patients
  8. Known active Hepatitis B or C
  9. Prior treatment with a PARP inhibitor
  10. Known history of myelodysplastic syndrome (MDS).
  11. known and persistent (>4 weeks) >/= grade 3 toxicity or fatigue from prior cancer treatment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   France,   Greece,   Hungary,   Iceland,   Israel,   Italy,   Netherlands,   Poland,   Portugal,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01905592
Other Study ID Numbers  ICMJE PR-30-5010-C
1307-BCG, BIG5-13 ( Other Identifier: EORTC, BIG )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Tesaro, Inc.
Study Sponsor  ICMJE Tesaro, Inc.
Collaborators  ICMJE
  • 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
Investigators  ICMJE
Study Chair: Nicholas Turner, MD Breast International Group
Study Chair: Judith Balmana, MD Hospital Vall d'Hebron
Principal Investigator: David Cameron, MD European Organisation for Research and Treatment of Cancer
Principal Investigator: John Erban, MD Tufts Medical Center
PRS Account Tesaro, Inc.
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP