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
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 300
- 试验地点
- 47
- 主要终点
- Time to the occurrence of any breast cancer (invasive or ductal carcinoma in situ [DCIS])
研究概览
简要总结
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.
详细描述
PRIMARY OBJECTIVE:
I. 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:
I. 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 25 Years 至 55 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
Arm A (denosumab)
Patients receive denosumab SC q6m for up to 5 years in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Arm A (denosumab)
Patients receive denosumab SC q6m for up to 5 years in the absence of disease progression or unacceptable toxicity.
干预措施: Denosumab (Drug)
Arm B (placebo)
Patients receive placebo SC q6m for up to 5 years in the absence of disease progression.
干预措施: Placebo (Drug)
Arm B (placebo)
Patients receive placebo SC q6m for up to 5 years in the absence of disease progression.
干预措施: Quality-of-Life Assessment (Other)
结局指标
主要结局
Time to the occurrence of any breast cancer (invasive or ductal carcinoma in situ [DCIS])
时间窗: From randomization to the occurrence of breast cancer (invasive or DCIS), assessed up to 5 years
Time to breast cancer (invasive or DCIS) will be compared between the two treatment arms using a stratified Cox proportional hazards regression model.
次要结局
- Time to ovarian, fallopian and peritoneal cancer (in women who have not undergone prophylactic bilateral salpingo-oophorectomy)(Up to 5 years post treatment)
- Time to invasive breast cancer(Up to 5 years post treatment)
- Time to invasive triple negative breast cancer(Up to 5 years post treatment)
- Time to other (nonbreast or ovarian cancer) malignancies, including those known to be associated with BRCA1 mutations(Up to 5 years post treatment)
- Time to clinical fractures in pre- and postmenopausal women(Up to 5 years post treatment)
- Frequency of breast biopsies(Up to 5 years post treatment)
- Frequency of benign breast lesions(Up to 5 years post treatment)
- Assess incidence, nature and severity of adverse events (AEs) using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0(Up to 5 years post treatment)