Studying the Effect of Denosumab on Preventing Breast Cancer in Women With a BRCA1 Germline Mutation (BRCA-P)

April 8, 2024 updated by: Alliance for Clinical Trials in Oncology

BRCA-P: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, International Phase 3 Study to Determine the Preventive Effect of Denosumab on Breast Cancer in Women Carrying a BRCA1 Germline Mutation

This phase III trial compares denosumab to placebo for the prevention of breast cancer in women with a BRCA1 germline mutation. A germline mutation is an inherited gene change which, in the BRCA1 gene, is associated with an increased risk of breast and other cancers. Denosumab is a monoclonal antibody that is used to treat bone loss in order to reduce the risk of bone fractures in healthy people, and to reduce new bone growths in cancer patients whose cancer has spread to their bones. Research has shown that denosumab may also reduce the risk of developing breast cancer in women carrying a BRCA1 germline mutation.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the reduction in the risk of any breast cancer (invasive or ductal carcinoma in situ [DCIS]) in women with germline BRCA1 mutation who are treated with denosumab compared to placebo.

SECONDARY OBJECTIVES:

I. To determine the reduction in the risk of invasive breast cancer in women with germline BRCA1 mutation who are treated with denosumab compared to placebo.

II. To determine the reduction in the risk of invasive triple negative breast cancer (TNBC) in women with germline BRCA1 mutation who are treated with denosumab compared to placebo.

III. To determine the reduction in risk of ovarian, fallopian and peritoneal cancers (in women who have not undergone prophylactic bilateral salpingo-oophorectomy [PBSO]) in women with germline BRCA1 mutation who are treated with denosumab compared to placebo.

IV. To determine the reduction in risk of other (i.e. non-breast and nonovarian) malignancies, including those known to be associated with BRCA1 germline mutations in women with germline BRCA1 mutation who are treated with denosumab compared to placebo.

V. To determine the reduction in the risk of clinical fractures in pre- and postmenopausal women with germline BRCA1 mutation who are treated with denosumab compared to placebo.

VI. To compare rates of breast biopsies and rate of benign breast lesions in women with germline BRCA1 mutation who are treated with denosumab compared to placebo.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive denosumab subcutaneously (SC) every 6 months (q6m) for up to 5 years in the absence of the development of breast cancer or unacceptable toxicity.

ARM B: Patients receive placebo SC q6m for up to 5 years in the absence of the development of breast cancer.

After completion of study treatment, patients are followed up every 12 months for 5 years.

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90033
        • Recruiting
        • USC / Norris Comprehensive Cancer Center
        • Principal Investigator:
          • Darcy V. Spicer
        • Contact:
          • Site Public Contact
          • Phone Number: 323-865-0451
      • San Francisco, California, United States, 94115
        • Recruiting
        • UCSF Medical Center-Mount Zion
        • Principal Investigator:
          • Pamela N. Munster
        • Contact:
          • Site Public Contact
          • Phone Number: 877-827-3222
    • Colorado
      • Aurora, Colorado, United States, 80012
        • Suspended
        • Rocky Mountain Cancer Centers-Aurora
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • UCHealth University of Colorado Hospital
        • Principal Investigator:
          • Marie E. Wood
        • Contact:
          • Site Public Contact
          • Phone Number: 720-848-0650
      • Boulder, Colorado, United States, 80304
        • Suspended
        • Rocky Mountain Cancer Centers-Boulder
      • Centennial, Colorado, United States, 80112
        • Suspended
        • Rocky Mountain Cancer Centers - Centennial
      • Denver, Colorado, United States, 80220
        • Recruiting
        • Rocky Mountain Cancer Centers-Rose
        • Principal Investigator:
          • Nicholas DiBella
        • Contact:
      • Denver, Colorado, United States, 80218
        • Suspended
        • Rocky Mountain Cancer Centers-Midtown
      • Englewood, Colorado, United States, 80113
        • Suspended
        • Rocky Mountain Cancer Centers - Swedish
      • Englewood, Colorado, United States, 80113
        • Suspended
        • Mountain Blue Cancer Care Center - Swedish
      • Littleton, Colorado, United States, 80120
        • Suspended
        • Rocky Mountain Cancer Centers-Littleton
      • Lone Tree, Colorado, United States, 80124
        • Suspended
        • Rocky Mountain Cancer Centers-Sky Ridge
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Recruiting
        • MedStar Georgetown University Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 202-444-2223
        • Principal Investigator:
          • Claudine Isaacs
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University
        • Principal Investigator:
          • Seema A. Khan
        • Contact:
      • Evanston, Illinois, United States, 60201
        • Recruiting
        • NorthShore University HealthSystem-Evanston Hospital
        • Principal Investigator:
          • Katharine A. Yao
        • Contact:
          • Site Public Contact
          • Phone Number: 847-570-2109
      • Highland Park, Illinois, United States, 60035
        • Suspended
        • NorthShore University HealthSystem-Highland Park Hospital
      • Urbana, Illinois, United States, 61801
        • Recruiting
        • Carle Cancer Center
        • Contact:
        • Principal Investigator:
          • Kendrith M. Rowland
    • Kansas
      • Overland Park, Kansas, United States, 66211
        • Suspended
        • University of Kansas Hospital-Indian Creek Campus
      • Westwood, Kansas, United States, 66205
        • Recruiting
        • University of Kansas Hospital-Westwood Cancer Center
        • Principal Investigator:
          • Lauren Nye
        • Contact:
    • Maine
      • South Portland, Maine, United States, 04106
        • Recruiting
        • Maine Medical Partners - South Portland
        • Principal Investigator:
          • Susan Miesfeldt
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
        • Principal Investigator:
          • Judy E. Garber
        • Contact:
          • Site Public Contact
          • Phone Number: 877-442-3324
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Beth Israel Deaconess Medical Center
        • Principal Investigator:
          • Nadine M. Tung
        • Contact:
          • Site Public Contact
          • Phone Number: 617-667-9925
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan Comprehensive Cancer Center
        • Principal Investigator:
          • Melissa L. Pilewskie
        • Contact:
          • Site Public Contact
          • Phone Number: 800-865-1125
      • Grand Rapids, Michigan, United States, 49503
        • Recruiting
        • Spectrum Health at Butterworth Campus
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Principal Investigator:
          • Sandhya Pruthi
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
      • Saint Paul, Minnesota, United States, 55101
        • Recruiting
        • Regions Hospital
        • Contact:
        • Principal Investigator:
          • Daniel M. Anderson
    • Nevada
      • Las Vegas, Nevada, United States, 89148
        • Recruiting
        • OptumCare Cancer Care at Fort Apache
        • Contact:
        • Principal Investigator:
          • John A. Ellerton
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
        • Principal Investigator:
          • Katherine D. Crew
        • Contact:
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Recruiting
        • Novant Health Presbyterian Medical Center
        • Contact:
        • Principal Investigator:
          • Lori F. Gentile
      • Greensboro, North Carolina, United States, 27403
        • Suspended
        • Novant Health Breast Surgery - Greensboro
      • Kernersville, North Carolina, United States, 27284
        • Suspended
        • Novant Health Cancer Institute - Kernersville
      • Mount Airy, North Carolina, United States, 27030
        • Suspended
        • Novant Health Cancer Institute - Mount Airy
      • Thomasville, North Carolina, United States, 27360
        • Suspended
        • Novant Health Cancer Institute - Thomasville
      • Winston-Salem, North Carolina, United States, 27103
        • Recruiting
        • Novant Health Forsyth Medical Center
        • Contact:
        • Principal Investigator:
          • Judith O. Hopkins
    • North Dakota
      • Fargo, North Dakota, United States, 58122
        • Active, not recruiting
        • Sanford Roger Maris Cancer Center
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Comprehensive Cancer Center
        • Principal Investigator:
          • Sagar D. Sardesai
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania/Abramson Cancer Center
        • Principal Investigator:
          • Susan M. Domchek
        • Contact:
          • Site Public Contact
          • Phone Number: 800-474-9892
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • University of Pittsburgh Cancer Institute (UPCI)
        • Principal Investigator:
          • Phuong L. Mai
        • Contact:
          • Site Public Contact
          • Phone Number: 412-647-8073
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • UT Southwestern/Simmons Cancer Center-Dallas
        • Contact:
        • Principal Investigator:
          • Rachel D. Wooldridge
      • Houston, Texas, United States, 77030
        • Recruiting
        • M D Anderson Cancer Center
        • Principal Investigator:
          • Isabelle Bedrosian
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute/University of Utah
        • Principal Investigator:
          • Sarah V. Colonna
        • Contact:
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • Virginia Commonwealth University/Massey Cancer Center
        • Principal Investigator:
          • Masey M. Ross
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Women with a confirmed deleterious or likely deleterious BRCA 1 germline mutation (variant class 4 or 5)
  • Age >= 25 years and =< 55 years at randomization
  • No evidence of breast cancer by MRI or mammography (MG) and clinical breast examination within the last 6 months prior to randomization
  • No clinical evidence of ovarian cancer at randomization
  • Negative pregnancy test at randomization for women of childbearing potential
  • No preventive breast surgery planned at time of randomization
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Written informed consent before any study-specific procedure is performed

Exclusion Criteria:

  • Prior bilateral mastectomy
  • History of ovarian cancer (including fallopian and peritoneal cancer)
  • History of breast cancer
  • History of invasive cancer except for basal cell or squamous cell skin cancer or carcinoma in situ of the cervix, stage 1 papillary or follicular thyroid cancer, atypical hyperplasia or LCIS (lobular carcinoma in situ)
  • Pregnant or lactating women (within the last 2 months prior to randomization)
  • Unwillingness to use highly effective contraception method during and within at least 5 months after cessation of denosumab/placebo therapy in women of childbearing potential. (Note: Women of childbearing potential should be monitored for pregnancy prior to each denosumab/placebo injection)

  • Clinically relevant hypocalcemia (history and current condition), or serum calcium < 2.0 mmol/L (< 8.0 mg/dL)

    * Hypocalcemia defined by calcium below the normal range (a single value below the normal range does not necessarily constitute hypocalcemia, but should be 'corrected' before dosing the subject). Monitoring of calcium level in regular intervals (usually prior to investigational product [IP] administration) is highly recommended

  • Tamoxifen, raloxifene or aromatase inhibitor use during the last 3 months prior to randomization or for a duration of more than 3 years in total (current and prior hormone replacement therapy [HRT] is permitted)
  • Prior use of denosumab
  • Subject has a known prior history or current evidence of osteonecrosis or osteomyelitis of the jaw, or an active dental/jaw condition which requires oral surgery including tooth extraction within 3 months of enrollment
  • Concurrent treatment with a bisphosphonate or an anti-angiogenic agent
  • Any major medical or psychiatric condition that may prevent the subject from completing the study
  • Known active infection with hepatitis B virus or hepatitis C virus
  • Known infection with human immunodeficiency virus (HIV)
  • Use of any other investigational product (current or prior aspirin or non-steroidal anti-inflammatory drugs [NSAIDs] are permitted)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A (denosumab)
Patients receive denosumab SC q6m for up to 5 years in the absence of disease progression or unacceptable toxicity.
Other: Quality-of-Life Assessment
Ancillary studies
Drug: Denosumab
Given SC
Placebo Comparator: Arm B (placebo)
Patients receive placebo SC q6m for up to 5 years in the absence of disease progression.
Other: Quality-of-Life Assessment
Ancillary studies
Drug: Placebo
Given SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to the occurrence of any breast cancer (invasive or ductal carcinoma in situ [DCIS])
Time Frame: From randomization to the occurrence of breast cancer (invasive or DCIS), assessed up to 5 years
Time to breast cancer (invasive or DCIS) will be compared between the two treatment arms using a stratified Cox proportional hazards regression model.
From randomization to the occurrence of breast cancer (invasive or DCIS), assessed up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to invasive breast cancer
Time Frame: Up to 5 years post treatment
Will be compared between the two treatment arms using a stratified Cox proportional hazards regression model.
Up to 5 years post treatment
Time to invasive triple negative breast cancer
Time Frame: Up to 5 years post treatment
Will be compared between the two treatment arms using a stratified Cox proportional hazards regression model.
Up to 5 years post treatment
Time to ovarian, fallopian and peritoneal cancer (in women who have not undergone prophylactic bilateral salpingo-oophorectomy)
Time Frame: Up to 5 years post treatment
Will be compared between the two treatment arms using a stratified Cox proportional hazards regression model. Time to ovarian cancer will be analyzed in the overall group and in different strata (oral contraceptive use, hormone replacement therapy use, and menopausal status).
Up to 5 years post treatment
Time to other (nonbreast or ovarian cancer) malignancies, including those known to be associated with BRCA1 mutations
Time Frame: Up to 5 years post treatment
Will be compared between the two treatment arms using a stratified Cox proportional hazards regression model.
Up to 5 years post treatment
Time to clinical fractures in pre- and postmenopausal women
Time Frame: Up to 5 years post treatment
Will be compared between the two treatment arms using a stratified Cox proportional hazards regression model.
Up to 5 years post treatment
Frequency of breast biopsies
Time Frame: Up to 5 years post treatment
May be recommended as part of care based on a finding on mammogram, MRI, ultrasound or physical exam performed as part of monitoring for breast cancer. Will be compared between the two treatment arms via chi-square analysis.
Up to 5 years post treatment
Frequency of benign breast lesions
Time Frame: Up to 5 years post treatment
May be recommended as part of care based on a finding on mammogram, MRI, ultrasound or physical exam performed as part of monitoring for breast cancer. Will be compared between the two treatment arms via chi-square analysis.
Up to 5 years post treatment
Assess incidence, nature and severity of adverse events (AEs) using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame: Up to 5 years post treatment
Overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment will be reported per treatment arm.
Up to 5 years post treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alliance for Clinical Trials in Oncology

Collaborators

National Cancer Institute (NCI)
Austrian Breast & Colorectal Cancer Study Group (ABCSG)

Investigators

  • Study Chair: Judy E. Garber, MD, MPH, Dana-Farber Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 14, 2023

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

December 1, 2033

Study Registration Dates

First Submitted

January 13, 2021

First Submitted That Met QC Criteria

January 13, 2021

First Posted (Actual)

January 15, 2021

Study Record Updates

Last Update Posted (Actual)

April 9, 2024

Last Update Submitted That Met QC Criteria

April 8, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A211801
  • UG1CA189823 (U.S. NIH Grant/Contract)
  • NCI-2020-11358 (Registry Identifier: NCI Clinical Trial Reporting Program)
  • 2017-002505-35 (EudraCT Number)
  • ABCSG 50 (Other Identifier: Austrian Breast & Colorectal Cancer Study Group)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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