NCI ID NCI-2020-11358
NCT ID NCT04711109
CTEP ID A211801
Primary Purpose PREVENTION
Anatomic Sites Breast
Minimum Age 25 Years
Maximum Age 55 Years
Gender FEMALE
Lead Org Alliance for Clinical Trials in Oncology
Principal Investigator Judy Ellen Garber
NCI Site View on ClinicalTrials.gov

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

Exclusion Criterea

  • 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)

Participating Clinics

OptumCare Cancer Care at Fort Apache


6190 South Fort Apache Road
Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org