Studying the Effect of Denosumab on Preventing Breast Cancer in Women with a BRCA1 Germline Mutation, the BRCA-P Trial
This phase III trial compares denosumab to usual care for the prevention of breast cancer in women with a BRCA1 germline mutation. A germline mutation is gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; germline mutations are passed on from parents to offspring. Denosumab is a monoclonal antibody that is used to treat bone loss in people who are at risk for bone fractures and for cancer patients whose cancer has spread to their bones. Denosumab may also decrease or prevent the risk of developing breast cancer in women carrying a BRCA1 germline mutation.
Eligibility
Inclusion Criterea
- 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
- Prior bilateral mastectomy
- History of ovarian cancer (including fallopian tube and primary peritoneal cancer)
- History of breast cancer
- History of invasive cancer except for basal cell or squamous cell skin cancer. History of the following are also allowed: carcinoma in situ of the cervix, stage 1 papillary or follicular thyroid cancer, atypical hyperplasia or lobular carcinoma in situ (LCIS)
- 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
- Clinically relevant hypocalcemia (history and current condition), or serum calcium < 2.0 mmol/L (< 8.0 mg/dL) or corrected calcium (< 2.1 mmol/L)
* 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 participant). 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)
- Any prior use of denosumab
- Participant 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 =< 3 months prior enrollment
- Concurrent treatment with a bisphosphonate or an anti-angiogenic agent (washout period for bisphosphonates [e.g. Zoledronic Acid] is up to 6 months, therefore these medications need to be stopped >= 6 months before first IP administration the latest)
- Concurrent therapy with other Investigational Products (at enrollment or during trial treatment)
- Any major medical or psychiatric condition that may prevent the participant from completing the study
- Known active infection with hepatitis B virus or hepatitis C virus
- Known infection with human immunodeficiency virus (HIV)
- Hypersensitivity to the active substance or to any of the excipients
- Known rare hereditary problems of fructose intolerance
Participating Clinics
OptumCare Cancer Care at Fort Apache
