Breast Cancer Clinical Trial

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

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.

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Full 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.

View Eligibility Criteria

Eligibility Criteria

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 is for people with:

Breast Cancer

Phase:

Phase 3

Estimated Enrollment:

300

Study ID:

NCT04711109

Recruitment Status:

Recruiting

Sponsor:

Alliance for Clinical Trials in Oncology

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There are 12 Locations for this study

See Locations Near You

Rocky Mountain Cancer Centers-Aurora
Aurora Colorado, 80012, United States More Info
Site Public Contact
Contact
303-777-2663
[email protected]
Nicholas DiBella
Principal Investigator
Rocky Mountain Cancer Centers-Boulder
Boulder Colorado, 80304, United States More Info
Site Public Contact
Contact
303-777-2663
[email protected]
Nicholas DiBella
Principal Investigator
Rocky Mountain Cancer Centers - Centennial
Centennial Colorado, 80112, United States More Info
Site Public Contact
Contact
303-777-2663
[email protected]
Nicholas DiBella
Principal Investigator
Rocky Mountain Cancer Centers-Midtown
Denver Colorado, 80218, United States More Info
Site Public Contact
Contact
303-777-2663
[email protected]
Nicholas DiBella
Principal Investigator
Rocky Mountain Cancer Centers-Rose
Denver Colorado, 80220, United States More Info
Site Public Contact
Contact
303-777-2663
[email protected]
Nicholas DiBella
Principal Investigator
Mountain Blue Cancer Care Center - Swedish
Englewood Colorado, 80113, United States More Info
Site Public Contact
Contact
303-777-2663
[email protected]
Nicholas DiBella
Principal Investigator
Rocky Mountain Cancer Centers - Swedish
Englewood Colorado, 80113, United States More Info
Site Public Contact
Contact
303-777-2663
[email protected]
Nicholas DiBella
Principal Investigator
Rocky Mountain Cancer Centers-Littleton
Littleton Colorado, 80120, United States
Rocky Mountain Cancer Centers-Sky Ridge
Lone Tree Colorado, 80124, United States More Info
Site Public Contact
Contact
303-777-2663
[email protected]
Nicholas DiBella
Principal Investigator
Carle Cancer Center
Urbana Illinois, 61801, United States More Info
Site Public Contact
Contact
800-446-5532
[email protected]
Kendrith M. Rowland
Principal Investigator
Mayo Clinic in Rochester
Rochester Minnesota, 55905, United States More Info
Site Public Contact
Contact
855-776-0015
Sandhya Pruthi
Principal Investigator
Sanford Roger Maris Cancer Center
Fargo North Dakota, 58122, United States More Info
Site Public Contact
Contact
701-234-6161
[email protected]
Preston D. Steen
Principal Investigator
M D Anderson Cancer Center
Houston Texas, 77030, United States More Info
Site Public Contact
Contact
877-632-6789
[email protected]
Isabelle Bedrosian
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 3

Estimated Enrollment:

300

Study ID:

NCT04711109

Recruitment Status:

Recruiting

Sponsor:


Alliance for Clinical Trials in Oncology

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