Prevention of breast cancer in women with a BRCA1 germline mutation MedDRA version: 21.0 Level: PT Classification code 10036898 Term: Prophylaxis System Organ Class: 10042613 - Surgical and medical procedures MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 23.0 Level: PT Classification code 10071980 Term: BRCA1 gene mutation System Organ Class: 100
Conditions
Sponsors
ABCSG (Austrian Breast & Colorectal Cancer Study Group)
Eligibility
Sex/Gender
All
Inclusion 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 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 2918 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • 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 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. • Clinically relevant hypocalcaemia (history and current condition), or serum calcium <2.0 mmol/L (<8.0 mg/dL) or corrected calcium (<2.1mmol/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 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 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 (wash out 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the reduction in the risk of any breast cancer (invasive or DCIS) in women with germline BRCA1 mutation who are treated with denosumab compared to placebo;Secondary Objective: • To determine the reduction in risk of invasive breast cancer • To determine the reduction in risk of invasive triple negative breast cancer (TNBC) • To determine the reduction in risk of ovarian, fallopian tube cancers (in women who have not undergone PBSO) and primary peritoneal cancers in women with germline BRCA1 mutation who are treated with denosumab compared to placebo • To determine the reduction in the risk of other (i.e. non-breast and non-ovarian) 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 • 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 • 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 ;Primary end point(s): • Time to the occurrence of any breast cancer (invasive or DCIS);Timepoint(s) of evaluation of this end point: The time from randomization to the occurrence of breast cancer (invasive or DCIS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Time to invasive breast cancer • Time to invasive triple negative breast cancer • Time to ovarian, fallopian tube or primary peritoneal cancer (in women who have not undergone PBSO) • Time to other (non breast or ovarian cancer) malignancies, including those known to be associated with BRCA1 mutations • Time to clinical fractures in pre- and postmenopausal women • Frequency of breast biopsies and frequency of benign breast lesions;Timepoint(s) of evaluation of this end point: Time-to-event | — |
Countries
Australia, Austria, Germany, Israel, Spain, United Kingdom, United States
Contacts
Public ContactTrial Office
ABCSG (Austrian Breast & Colorectal Cancer Study Group)
Outcome results
None listed