Studying the Effect of Denosumab on Preventing Breast Cancer in Women With a BRCA1 Germline Mutation

NCT ID: NCT04711109

Last Updated: 2025-04-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-14

Study Completion Date

2033-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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BRCA1 Mutation Breast Cancer Breast Diseases Breast Neoplasms Breast Carcinoma Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Arm A (denosumab)

Patients receive denosumab SC q6m for up to 5 years in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Denosumab

Intervention Type DRUG

Given SC

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Arm B (placebo)

Patients receive placebo SC q6m for up to 5 years in the absence of disease progression.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Given SC

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Interventions

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Denosumab

Given SC

Intervention Type DRUG

Placebo

Given SC

Intervention Type DRUG

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Eligibility Criteria

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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)
Minimum Eligible Age

25 Years

Maximum Eligible Age

55 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Austrian Breast & Colorectal Cancer Study Group (ABCSG)

UNKNOWN

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Judy E. Garber, MD, MPH

Role: STUDY_CHAIR

Dana-Farber Cancer Institute

Locations

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USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

UCSF Medical Center-Mount Zion

San Francisco, California, United States

Site Status

Rocky Mountain Cancer Centers-Aurora

Aurora, Colorado, United States

Site Status

UCHealth University of Colorado Hospital

Aurora, Colorado, United States

Site Status

Rocky Mountain Cancer Centers-Boulder

Boulder, Colorado, United States

Site Status

Rocky Mountain Cancer Centers - Centennial

Centennial, Colorado, United States

Site Status

Rocky Mountain Cancer Centers-Midtown

Denver, Colorado, United States

Site Status

Rocky Mountain Cancer Centers-Rose

Denver, Colorado, United States

Site Status

Mountain Blue Cancer Care Center - Swedish

Englewood, Colorado, United States

Site Status

Rocky Mountain Cancer Centers - Swedish

Englewood, Colorado, United States

Site Status

Rocky Mountain Cancer Centers-Littleton

Littleton, Colorado, United States

Site Status

Rocky Mountain Cancer Centers-Sky Ridge

Lone Tree, Colorado, United States

Site Status

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, United States

Site Status

NorthShore University HealthSystem-Highland Park Hospital

Highland Park, Illinois, United States

Site Status

Carle Cancer Center

Urbana, Illinois, United States

Site Status

University of Kansas Hospital-Indian Creek Campus

Overland Park, Kansas, United States

Site Status

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, United States

Site Status

Maine Medical Center- Scarborough Campus

Scarborough, Maine, United States

Site Status

Maine Medical Partners - South Portland

South Portland, Maine, United States

Site Status

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Corewell Health Grand Rapids Hospitals - Butterworth Hospital

Grand Rapids, Michigan, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

Regions Hospital

Saint Paul, Minnesota, United States

Site Status

OptumCare Cancer Care at Fort Apache

Las Vegas, Nevada, United States

Site Status

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Site Status

Novant Health Breast Surgery - Greensboro

Greensboro, North Carolina, United States

Site Status

Novant Health Cancer Institute - Kernersville

Kernersville, North Carolina, United States

Site Status

Novant Health Cancer Institute - Mount Airy

Mount Airy, North Carolina, United States

Site Status

Novant Health Cancer Institute - Thomasville

Thomasville, North Carolina, United States

Site Status

Novant Health Forsyth Medical Center

Winston-Salem, North Carolina, United States

Site Status

Sanford Roger Maris Cancer Center

Fargo, North Dakota, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States

Site Status

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Site Status

University of Vermont Medical Center

Burlington, Vermont, United States

Site Status

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2020-11358

Identifier Type: REGISTRY

Identifier Source: secondary_id

UG1CA189823

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2017-002505-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ABCSG 50

Identifier Type: OTHER

Identifier Source: secondary_id

A211801

Identifier Type: -

Identifier Source: org_study_id

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