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

NCT04711109 | Active Not Recruiting Phase 3 DMC FDA Drug

• 5 other identifiers: A211801NCI-2020-11358UG1CA1898232017-002505-35ABCSG 50
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 47

Brief Summary

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.

Conditions

BRCA1 Mutation; Breast Cancer; Breast Diseases; Breast Neoplasms; Breast Carcinoma; Neoplasms

Keywords

RANKL; Breast Cancer Prevention; Denosumab; Bone Density Conservation Agents; Physiological Effects of Drugs

Outcome Measures

Primary Outcomes (1)

• Time to the occurrence of any breast cancer (invasive or ductal carcinoma in situ [DCIS])

  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 Outcomes (8)

• Time to invasive breast cancer

  Up to 5 years post treatment

• Time to invasive triple negative breast cancer

  Up to 5 years post treatment

• Time to ovarian, fallopian and peritoneal cancer (in women who have not undergone prophylactic bilateral salpingo-oophorectomy)

  Up to 5 years post treatment

• Time to other (nonbreast or ovarian cancer) malignancies, including those known to be associated with BRCA1 mutations

  Up to 5 years post treatment

• Time to clinical fractures in pre- and postmenopausal women

  Up to 5 years post treatment

Study Arms (2)

Arm A (denosumab)

EXPERIMENTAL

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

Drug: Denosumab; Other: Quality-of-Life Assessment

Arm B (placebo)

PLACEBO COMPARATOR

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

Drug: Placebo; Other: Quality-of-Life Assessment

Interventions

Denosumab DRUG

Given SC

Arm A (denosumab)

Placebo DRUG

Given SC

Arm B (placebo)

Quality-of-Life Assessment OTHER

Ancillary studies

Arm A (denosumab); Arm B (placebo)

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator
• Austrian Breast & Colorectal Cancer Study Group (ABCSG): collaborator

Study Sites (47)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UCSF Medical Center-Mount Zion

San Francisco, California, 94115, United States

Location

Rocky Mountain Cancer Centers-Aurora

Aurora, Colorado, 80012, United States

Location

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Cancer Centers-Boulder

Boulder, Colorado, 80304, United States

Location

Rocky Mountain Cancer Centers - Centennial

Centennial, Colorado, 80112, United States

Location

Rocky Mountain Cancer Centers-Midtown

Denver, Colorado, 80218, United States

Location

Rocky Mountain Cancer Centers-Rose

Denver, Colorado, 80220, United States

Location

Mountain Blue Cancer Care Center - Swedish

Englewood, Colorado, 80113, United States

Location

Rocky Mountain Cancer Centers - Swedish

Englewood, Colorado, 80113, United States

Location

Rocky Mountain Cancer Centers-Littleton

Littleton, Colorado, 80120, United States

Location

Rocky Mountain Cancer Centers-Sky Ridge

Lone Tree, Colorado, 80124, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

NorthShore University HealthSystem-Highland Park Hospital

Highland Park, Illinois, 60035, United States

Location

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

University of Kansas Hospital-Indian Creek Campus

Overland Park, Kansas, 66211, United States

Location

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

Location

Maine Medical Center- Scarborough Campus

Scarborough, Maine, 04074, United States

Location

Maine Medical Partners - South Portland

South Portland, Maine, 04106, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Corewell Health Grand Rapids Hospitals - Butterworth Hospital

Grand Rapids, Michigan, 49503, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

OptumCare Cancer Care at Fort Apache

Las Vegas, Nevada, 89148, United States

Location

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

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, 28204, United States

Location

Novant Health Breast Surgery - Greensboro

Greensboro, North Carolina, 27403, United States

Location

Novant Health Cancer Institute - Kernersville

Kernersville, North Carolina, 27284, United States

Location

Novant Health Cancer Institute - Mount Airy

Mount Airy, North Carolina, 27030, United States

Location

Novant Health Cancer Institute - Thomasville

Thomasville, North Carolina, 27360, United States

Location

Novant Health Forsyth Medical Center

Winston-Salem, North Carolina, 27103, United States

Location

Sanford Roger Maris Cancer Center

Fargo, North Dakota, 58122, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Breast Diseases; Neoplasms

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Judy E. Garber, MD, MPH

  Dana-Farber Cancer Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2021
• First Posted: January 15, 2021
• Study Start: February 14, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2033
• Last Updated: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

US (47)