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研究狄诺塞麦对 BRCA1 种系突变女性预防乳腺癌的作用 (BRCA-P)

2026年10月1日 更新者：Alliance for Clinical Trials in Oncology

BRCA-P：一项随机、双盲、安慰剂对照、多中心、国际 3 期研究，以确定狄诺塞麦对携带 BRCA1 种系突变的女性乳腺癌的预防作用

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.

研究概览

地位

主动，不招人

条件

干预/治疗

详细说明

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.

III. To determine the reduction in risk of ovarian, fallopian and peritoneal cancers (in women who have not undergone prophylactic bilateral salpingo-oophorectomy [PBSO]) in women with germline BRCA1 mutation who are treated with denosumab compared to placebo.

IV. To determine the reduction in risk of other (i.e. non-breast and nonovarian) 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.

V. 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.

VI. 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.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive denosumab subcutaneously (SC) every 6 months (q6m) for up to 5 years in the absence of the development of breast cancer or unacceptable toxicity.

ARM B: Patients receive placebo SC q6m for up to 5 years in the absence of the development of breast cancer.

After completion of study treatment, patients are followed up every 12 months for 5 years.

研究类型

介入性

注册 (估计的)

300

阶段

  • 第三阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 美国
    • California
      • Los Angeles、California、美国、90033
        • USC / Norris Comprehensive Cancer Center
      • San Francisco、California、美国、94115
        • UCSF Medical Center-Mount Zion
    • Colorado
      • Aurora、Colorado、美国、80012
        • Rocky Mountain Cancer Centers-Aurora
      • Aurora、Colorado、美国、80045
        • UCHealth University of Colorado Hospital
      • Boulder、Colorado、美国、80304
        • Rocky Mountain Cancer Centers-Boulder
      • Centennial、Colorado、美国、80112
        • Rocky Mountain Cancer Centers - Centennial
      • Denver、Colorado、美国、80218
        • Rocky Mountain Cancer Centers-Midtown
      • Denver、Colorado、美国、80220
        • Rocky Mountain Cancer Centers-Rose
      • Englewood、Colorado、美国、80113
        • Mountain Blue Cancer Care Center - Swedish
      • Englewood、Colorado、美国、80113
        • Rocky Mountain Cancer Centers - Swedish
      • Littleton、Colorado、美国、80120
        • Rocky Mountain Cancer Centers-Littleton
      • Lone Tree、Colorado、美国、80124
        • Rocky Mountain Cancer Centers-Sky Ridge
    • District of Columbia
      • Washington D.C.、District of Columbia、美国、20007
        • MedStar Georgetown University Hospital
    • Illinois
      • Chicago、Illinois、美国、60611
        • Northwestern University
      • Chicago、Illinois、美国、60637
        • University of Chicago Comprehensive Cancer Center
      • Evanston、Illinois、美国、60201
        • NorthShore University HealthSystem-Evanston Hospital
      • Highland Park、Illinois、美国、60035
        • NorthShore University HealthSystem-Highland Park Hospital
      • Urbana、Illinois、美国、61801
        • Carle Cancer Center
    • Kansas
      • Overland Park、Kansas、美国、66211
        • University of Kansas Hospital-Indian Creek Campus
      • Westwood、Kansas、美国、66205
        • University of Kansas Hospital-Westwood Cancer Center
    • Maine
      • Scarborough、Maine、美国、04074
        • Maine Medical Center- Scarborough Campus
      • South Portland、Maine、美国、04106
        • Maine Medical Partners - South Portland
    • Maryland
      • Baltimore、Maryland、美国、21287
        • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Massachusetts
      • Boston、Massachusetts、美国、02215
        • Beth Israel Deaconess Medical Center
      • Boston、Massachusetts、美国、02215
        • Dana-Farber Cancer Institute
    • Michigan
      • Ann Arbor、Michigan、美国、48109
        • University of Michigan Comprehensive Cancer Center
      • Grand Rapids、Michigan、美国、49503
        • Corewell Health Grand Rapids Hospitals - Butterworth Hospital
    • Minnesota
      • Rochester、Minnesota、美国、55905
        • Mayo Clinic in Rochester
      • Saint Paul、Minnesota、美国、55101
        • Regions Hospital
    • Nevada
      • Las Vegas、Nevada、美国、89148
        • OptumCare Cancer Care at Fort Apache
    • New York
      • New York、New York、美国、10065
        • Memorial Sloan Kettering Cancer Center
      • New York、New York、美国、10032
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
    • North Carolina
      • Charlotte、North Carolina、美国、28204
        • Novant Health Presbyterian Medical Center
      • Greensboro、North Carolina、美国、27403
        • Novant Health Breast Surgery - Greensboro
      • Kernersville、North Carolina、美国、27284
        • Novant Health Cancer Institute - Kernersville
      • Mount Airy、North Carolina、美国、27030
        • Novant Health Cancer Institute - Mount Airy
      • Thomasville、North Carolina、美国、27360
        • Novant Health Cancer Institute - Thomasville
      • Winston-Salem、North Carolina、美国、27103
        • Novant Health Forsyth Medical Center
    • North Dakota
      • Fargo、North Dakota、美国、58122
        • Sanford Roger Maris Cancer Center
    • Ohio
      • Columbus、Ohio、美国、43210
        • Ohio State University Comprehensive Cancer Center
    • Pennsylvania
      • Philadelphia、Pennsylvania、美国、19104
        • University of Pennsylvania/Abramson Cancer Center
      • Pittsburgh、Pennsylvania、美国、15232
        • University of Pittsburgh Cancer Institute (UPCI)
    • Texas
      • Dallas、Texas、美国、75390
        • UT Southwestern/Simmons Cancer Center-Dallas
      • Houston、Texas、美国、77030
        • M D Anderson Cancer Center
    • Utah
      • Salt Lake City、Utah、美国、84112
        • Huntsman Cancer Institute/University of Utah
    • Vermont
      • Burlington、Vermont、美国、05401
        • University of Vermont Medical Center
    • Virginia
      • Richmond、Virginia、美国、23298
        • Virginia Commonwealth University/Massey Cancer Center

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

25年 至 55年 (成人)

接受健康志愿者

是的

有资格学习的性别

女性

描述

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)

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：预防
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：双倍的

武器和干预

参与者组/臂
干预/治疗
实验性的：Arm A (denosumab)

Patients receive denosumab SC q6m for up to 5 years in the absence of disease progression or unacceptable toxicity.
其他：Quality-of-Life Assessment

Ancillary studies

药品：Denosumab

Given SC
安慰剂比较：Arm B (placebo)

Patients receive placebo SC q6m for up to 5 years in the absence of disease progression.
其他：Quality-of-Life Assessment

Ancillary studies

药品：Placebo

Given SC

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Time to the occurrence of any breast cancer (invasive or ductal carcinoma in situ [DCIS])
大体时间：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.
From randomization to the occurrence of breast cancer (invasive or DCIS), assessed up to 5 years

次要结果测量

结果测量
措施说明
大体时间
Time to invasive breast cancer
大体时间：Up to 5 years post treatment

Will be compared between the two treatment arms using a stratified Cox proportional hazards regression model.
Up to 5 years post treatment
Time to invasive triple negative breast cancer
大体时间：Up to 5 years post treatment

Will be compared between the two treatment arms using a stratified Cox proportional hazards regression model.
Up to 5 years post treatment
Time to ovarian, fallopian and peritoneal cancer (in women who have not undergone prophylactic bilateral salpingo-oophorectomy)
大体时间：Up to 5 years post treatment

Will be compared between the two treatment arms using a stratified Cox proportional hazards regression model. Time to ovarian cancer will be analyzed in the overall group and in different strata (oral contraceptive use, hormone replacement therapy use, and menopausal status).
Up to 5 years post treatment
Time to other (nonbreast or ovarian cancer) malignancies, including those known to be associated with BRCA1 mutations
大体时间：Up to 5 years post treatment

Will be compared between the two treatment arms using a stratified Cox proportional hazards regression model.
Up to 5 years post treatment
Time to clinical fractures in pre- and postmenopausal women
大体时间：Up to 5 years post treatment

Will be compared between the two treatment arms using a stratified Cox proportional hazards regression model.
Up to 5 years post treatment
Frequency of breast biopsies
大体时间：Up to 5 years post treatment

May be recommended as part of care based on a finding on mammogram, MRI, ultrasound or physical exam performed as part of monitoring for breast cancer. Will be compared between the two treatment arms via chi-square analysis.
Up to 5 years post treatment
Frequency of benign breast lesions
大体时间：Up to 5 years post treatment

May be recommended as part of care based on a finding on mammogram, MRI, ultrasound or physical exam performed as part of monitoring for breast cancer. Will be compared between the two treatment arms via chi-square analysis.
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
大体时间：Up to 5 years post treatment

Overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment will be reported per treatment arm.
Up to 5 years post treatment

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Alliance for Clinical Trials in Oncology

合作者

National Cancer Institute (NCI)
Austrian Breast & Colorectal Cancer Study Group

调查人员

  • 学习椅：Judy E. Garber, MD, MPH、Dana-Farber Cancer Institute

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2023年2月14日

初级完成 (估计的)

2027年7月1日

研究完成 (估计的)

2033年12月1日

研究注册日期

首次提交

2021年1月13日

首先提交符合 QC 标准的

2021年1月13日

首次发布 (实际的)

2021年1月15日

研究记录更新

最后更新发布 (实际的)

2026年10月5日

上次提交的符合 QC 标准的更新

2026年10月1日

最后验证

2026年10月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • A211801
  • UG1CA189823 (美国 NIH 拨款/合同)
  • NCI-2020-11358 (注册表标识符：NCI Clinical Trial Reporting Program)
  • 2017-002505-35 (EudraCT编号)
  • ABCSG 50 (其他标识符：Austrian Breast & Colorectal Cancer Study Group)
  • 2017 (美国 NIH 拨款/合同)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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