Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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.

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

Condition or disease Intervention/treatment 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

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 306 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : October 2013
Estimated Primary Completion Date : May 2018
Estimated Study Completion Date : May 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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


Other Outcome Measures:
  1. 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



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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/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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01905592


  Hide Study Locations
Locations
Layout table for location information
United States, Arizona
Tucson, Arizona, United States
United States, California
Los Angeles, California, United States
United States, Florida
Fort Myers, Florida, United States
Miami, Florida, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, Minnesota
Minneapolis, Minnesota, United States
United States, Nebraska
Omaha, Nebraska, United States
United States, Nevada
Henderson, Nevada, United States
United States, New York
Lake Success, New York, United States
Latham, New York, United States
United States, Oregon
Eugene, Oregon, United States
Portland, Oregon, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Tennessee
Nashville, Tennessee, United States
United States, Texas
Dallas, Texas, United States
Fort Worth, Texas, United States, 76104
Plano, Texas, United States, 75075
San Antonio, Texas, United States
Webster, Texas, United States
Weslaco, Texas, United States
United States, Virginia
Low Moor, Virginia, United States
United States, Washington
Everett, Washington, United States
Seattle, Washington, United States
United States, Wisconsin
Milwaukee, Wisconsin, United States
Belgium
Aalst, Belgium
Brussels, Belgium
Edegem, Belgium
Liege, Belgium
Namur, Belgium
Canada, Alberta
Calgary, Alberta, Canada
Canada, British Columbia
Kelowna, British Columbia, Canada
Canada, Ontario
Toronto, Ontario, Canada
Canada, Quebec
Montreal, Quebec, Canada
France
Bordeaux, France
Dijon, France
Lille, France
Lyon, France
Montpellier, France
Nantes, France
Paris, France
Saint-Cloud, France
Greece
Athens, Greece
Heraklion, Greece
Nea Kifisia, Greece
Neo Faliro, Greece
Thessaloniki, Greece
Hungary
Budapest, Hungary
Debrecen, Hungary
Miskolc, Hungary
Nyíregyháza, Hungary
Szeged, Hungary
Iceland
Reykjavik, Iceland
Israel
Haifa, Israel
Holon, Israel
Jerusalem, Israel
Kfar-Saba, Israel
Rehovot, Israel
Tel Aviv, Israel
Tel Hashomer, Israel
Italy
Ancona, Italy
Cattolica, Italy
Cremona, Italy
Genova, Italy
Lecce, Italy
Legnago, Italy
Meldola, Italy
Milan, Italy
Parma, Italy
Prato, Italy
Rimini, Italy
Viterbo, Italy
Netherlands
Maastricht, Limburg, Netherlands
Leiden, Netherlands
Zwolle, Netherlands
Poland
Lodz, Poland
Raciborz, Poland
Portugal
Coimbra, Portugal
Lisboa, Portugal
Porto, Portugal
Spain
Barcelona, Spain
Cáceres, Spain
Lleida, Spain
Lugo, Spain
Madrid, Spain
Pamplona, Spain
Valencia, Spain
United Kingdom
Bebington, United Kingdom
Belfast, United Kingdom
Cardiff, United Kingdom
Edinburgh, United Kingdom
Glasgow, United Kingdom
Headington, United Kingdom
London, United Kingdom
Northwood, United Kingdom
Nottingham, United Kingdom
Southampton, United Kingdom
Surrey, United Kingdom
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
Investigators
Layout table for investigator information
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

Additional Information:
Layout table for additonal information
Responsible Party: Tesaro, Inc.
ClinicalTrials.gov Identifier: NCT01905592     History of Changes
Other Study ID Numbers: PR-30-5010-C
1307-BCG, BIG5-13 ( Other Identifier: EORTC, BIG )
First Posted: July 23, 2013    Key Record Dates
Last Update Posted: November 6, 2017
Last Verified: October 2017

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:
Layout table for MeSH terms
Carcinoma
Breast Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Niraparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents