Studying the Effect of Denosumab on Preventing Breast Cancer in Women With a BRCA1 Germline Mutation (BRCA-P)
BRCA1 Mutation, Breast Cancer, Breast Diseases
About this trial
This is an interventional prevention trial for BRCA1 Mutation focused on measuring RANKL, Breast Cancer Prevention, Denosumab, Bone Density Conservation Agents, Physiological Effects of Drugs
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)
Sites / Locations
- USC / Norris Comprehensive Cancer CenterRecruiting
- UCSF Medical Center-Mount ZionRecruiting
- Rocky Mountain Cancer Centers-Aurora
- University of Colorado HospitalRecruiting
- Rocky Mountain Cancer Centers-Boulder
- Rocky Mountain Cancer Centers - Centennial
- Rocky Mountain Cancer Centers-Midtown
- Rocky Mountain Cancer Centers-RoseRecruiting
- Mountain Blue Cancer Care Center - Swedish
- Rocky Mountain Cancer Centers - Swedish
- Rocky Mountain Cancer Centers-Littleton
- Rocky Mountain Cancer Centers-Sky Ridge
- MedStar Georgetown University HospitalRecruiting
- Northwestern UniversityRecruiting
- NorthShore University HealthSystem-Evanston HospitalRecruiting
- NorthShore University HealthSystem-Highland Park Hospital
- Carle Cancer CenterRecruiting
- University of Kansas Hospital-Indian Creek Campus
- University of Kansas Hospital-Westwood Cancer CenterRecruiting
- Maine Medical Partners - South PortlandRecruiting
- Beth Israel Deaconess Medical CenterRecruiting
- Dana-Farber Cancer InstituteRecruiting
- Spectrum Health at Butterworth CampusRecruiting
- Mayo Clinic in RochesterRecruiting
- Regions HospitalRecruiting
- OptumCare Cancer Care at Fort ApacheRecruiting
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer CenterRecruiting
- Novant Health Presbyterian Medical CenterRecruiting
- Novant Health Breast Surgery - Greensboro
- Novant Health Cancer Institute - Kernersville
- Novant Health Cancer Institute - Mount Airy
- Novant Health Cancer Institute - Thomasville
- Novant Health Forsyth Medical CenterRecruiting
- Sanford Roger Maris Cancer Center
- Ohio State University Comprehensive Cancer CenterRecruiting
- University of Pennsylvania/Abramson Cancer CenterRecruiting
- University of Pittsburgh Cancer Institute (UPCI)Recruiting
- M D Anderson Cancer CenterRecruiting
- Huntsman Cancer Institute/University of UtahRecruiting
- Virginia Commonwealth University/Massey Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Arm A (denosumab)
Arm B (placebo)
Patients receive denosumab SC q6m for up to 5 years in the absence of disease progression or unacceptable toxicity.
Patients receive placebo SC q6m for up to 5 years in the absence of disease progression.