NCT04711109

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

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

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 300 (estimated)
• Sponsor: Alliance for Clinical Trials in Oncology · Academic / Other
• Sex: Female
• Age: 25 Years – 55 Years
• Healthy volunteers: Accepted

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.

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.

Conditions

• BRCA1 Mutation
• Breast Cancer
• Breast Diseases
• Breast Neoplasms
• Breast Carcinoma
• Neoplasms

Interventions

Type	Name	Description
DRUG	Denosumab	Given SC
DRUG	Placebo	Given SC
OTHER	Quality-of-Life Assessment	Ancillary studies

Timeline

• Start date: 2023-02-14
• Primary completion: 2027-07-01
• Completion: 2033-12-01
• First posted: 2021-01-15
• Last updated: 2025-04-02

Locations

47 sites across 1 country: United States

Regulatory

• FDA-regulated drug study