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

  • STATUS
    Recruiting
  • End date
    Dec 28, 2033
  • participants needed
    300
  • sponsor
    Alliance for Clinical Trials in Oncology
Updated on 28 July 2022
cancer
breast surgery
monoclonal antibodies
breast cancer
primary cancer
BRCA1
mammogram
Accepts healthy volunteers

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.

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.

Details
Condition BRCA1 Mutation, Breast Cancer, Breast Diseases, Breast Neoplasms, Breast Carcinoma, Neoplasms
Treatment quality-of-life assessment, Placebo, Denosumab
Clinical Study IdentifierNCT04711109
SponsorAlliance for Clinical Trials in Oncology
Last Modified on28 July 2022

Eligibility

Yes No Not Sure

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)
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