This study is in progress, not accepting new patients

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

a study on BRCA 1 Gene Mutation Breast Cancer Neoplasms

Summary

Eligibility
for females ages 25-55 (full criteria)
Healthy Volunteers
healthy people welcome
Location
at San Francisco, California and other locations
Dates
study started
completion around

Description

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.

Official Title

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

Details

PRIMARY OBJECTIVE:

  1. 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:

  1. 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.

  1. 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.

Keywords

BRCA1 Mutation, Breast Cancer, Breast Diseases, Breast Neoplasms, Breast Carcinoma, Neoplasms, RANKL, Breast Cancer Prevention, Denosumab, Bone Density Conservation Agents, Physiological Effects of Drugs, Quality-of-Life Assessment

Eligibility

You can join if…

Open to females ages 25-55

  • 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 CAN'T join 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)
  • Use of any other investigational product (current or prior aspirin or non-steroidal anti-inflammatory drugs [NSAIDs] are permitted)

Locations

  • UCSF Medical Center-Mount Zion
    San Francisco California 94115 United States
  • USC / Norris Comprehensive Cancer Center
    Los Angeles California 90033 United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Alliance for Clinical Trials in Oncology
ID
NCT04711109
Phase
Phase 3 research study
Study Type
Interventional
Participants
Expecting 300 study participants
Last Updated