BRCA1 生殖細胞変異を持つ女性の乳がん予防に対するデノスマブの効果の研究 (BRCA-P)
BRCA-P: BRCA1 生殖細胞変異を有する女性の乳癌に対するデノスマブの予防効果を決定するための無作為化、二重盲検、プラセボ対照、多施設、国際第 3 相試験
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.
調査の概要
状態
詳細な説明
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.
研究の種類
入学 (推定)
段階
- フェーズ 3
連絡先と場所
研究場所
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California
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Los Angeles、California、アメリカ、90033
- USC / Norris Comprehensive Cancer Center
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San Francisco、California、アメリカ、94115
- UCSF Medical Center-Mount Zion
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Colorado
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Aurora、Colorado、アメリカ、80012
- Rocky Mountain Cancer Centers-Aurora
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Aurora、Colorado、アメリカ、80045
- UCHealth University of Colorado Hospital
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Boulder、Colorado、アメリカ、80304
- Rocky Mountain Cancer Centers-Boulder
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Centennial、Colorado、アメリカ、80112
- Rocky Mountain Cancer Centers - Centennial
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Denver、Colorado、アメリカ、80218
- Rocky Mountain Cancer Centers-Midtown
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Denver、Colorado、アメリカ、80220
- Rocky Mountain Cancer Centers-Rose
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Englewood、Colorado、アメリカ、80113
- Mountain Blue Cancer Care Center - Swedish
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Englewood、Colorado、アメリカ、80113
- Rocky Mountain Cancer Centers - Swedish
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Littleton、Colorado、アメリカ、80120
- Rocky Mountain Cancer Centers-Littleton
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Lone Tree、Colorado、アメリカ、80124
- Rocky Mountain Cancer Centers-Sky Ridge
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District of Columbia
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Washington D.C.、District of Columbia、アメリカ、20007
- MedStar Georgetown University Hospital
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Illinois
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Chicago、Illinois、アメリカ、60611
- Northwestern University
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Chicago、Illinois、アメリカ、60637
- University of Chicago Comprehensive Cancer Center
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Evanston、Illinois、アメリカ、60201
- NorthShore University HealthSystem-Evanston Hospital
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Highland Park、Illinois、アメリカ、60035
- NorthShore University HealthSystem-Highland Park Hospital
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Urbana、Illinois、アメリカ、61801
- Carle Cancer Center
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Kansas
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Overland Park、Kansas、アメリカ、66211
- University of Kansas Hospital-Indian Creek Campus
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Westwood、Kansas、アメリカ、66205
- University of Kansas Hospital-Westwood Cancer Center
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Maine
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Scarborough、Maine、アメリカ、04074
- Maine Medical Center- Scarborough Campus
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South Portland、Maine、アメリカ、04106
- Maine Medical Partners - South Portland
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Maryland
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Baltimore、Maryland、アメリカ、21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
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Massachusetts
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Boston、Massachusetts、アメリカ、02215
- Beth Israel Deaconess Medical Center
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Boston、Massachusetts、アメリカ、02215
- Dana-Farber Cancer Institute
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Michigan
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Ann Arbor、Michigan、アメリカ、48109
- University of Michigan Comprehensive Cancer Center
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Grand Rapids、Michigan、アメリカ、49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
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Minnesota
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Rochester、Minnesota、アメリカ、55905
- Mayo Clinic in Rochester
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Saint Paul、Minnesota、アメリカ、55101
- Regions Hospital
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Nevada
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Las Vegas、Nevada、アメリカ、89148
- OptumCare Cancer Care at Fort Apache
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New York
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New York、New York、アメリカ、10065
- Memorial Sloan Kettering Cancer Center
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New York、New York、アメリカ、10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
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North Carolina
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Charlotte、North Carolina、アメリカ、28204
- Novant Health Presbyterian Medical Center
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Greensboro、North Carolina、アメリカ、27403
- Novant Health Breast Surgery - Greensboro
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Kernersville、North Carolina、アメリカ、27284
- Novant Health Cancer Institute - Kernersville
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Mount Airy、North Carolina、アメリカ、27030
- Novant Health Cancer Institute - Mount Airy
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Thomasville、North Carolina、アメリカ、27360
- Novant Health Cancer Institute - Thomasville
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Winston-Salem、North Carolina、アメリカ、27103
- Novant Health Forsyth Medical Center
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North Dakota
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Fargo、North Dakota、アメリカ、58122
- Sanford Roger Maris Cancer Center
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Ohio
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Columbus、Ohio、アメリカ、43210
- Ohio State University Comprehensive Cancer Center
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19104
- University of Pennsylvania/Abramson Cancer Center
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Pittsburgh、Pennsylvania、アメリカ、15232
- University of Pittsburgh Cancer Institute (UPCI)
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Texas
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Dallas、Texas、アメリカ、75390
- UT Southwestern/Simmons Cancer Center-Dallas
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Houston、Texas、アメリカ、77030
- M D Anderson Cancer Center
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Utah
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Salt Lake City、Utah、アメリカ、84112
- Huntsman Cancer Institute/University of Utah
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Vermont
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Burlington、Vermont、アメリカ、05401
- University of Vermont Medical Center
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Virginia
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Richmond、Virginia、アメリカ、23298
- Virginia Commonwealth University/Massey Cancer Center
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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:
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Prior bilateral mastectomy
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History of ovarian cancer (including fallopian and peritoneal cancer)
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History of breast cancer
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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)
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Pregnant or lactating women (within the last 2 months prior to randomization)
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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)
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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
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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)
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Prior use of denosumab
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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
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Concurrent treatment with a bisphosphonate or an anti-angiogenic agent
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Any major medical or psychiatric condition that may prevent the subject from completing the study
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Known active infection with hepatitis B virus or hepatitis C virus
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Known infection with human immunodeficiency virus (HIV)
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Use of any other investigational product (current or prior aspirin or non-steroidal anti-inflammatory drugs [NSAIDs] are permitted)
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：防止
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Arm A (denosumab)
Patients receive denosumab SC q6m for up to 5 years in the absence of disease progression or unacceptable toxicity. |
Ancillary studies Given SC |
|
プラセボコンパレーター：Arm B (placebo)
Patients receive placebo SC q6m for up to 5 years in the absence of disease progression. |
Ancillary studies Given SC |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Time to the occurrence of any breast cancer (invasive or ductal carcinoma in situ [DCIS])
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Time to invasive breast cancer
時間枠：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
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
協力者と研究者
捜査官
- スタディチェア：Judy E. Garber, MD, MPH、Dana-Farber Cancer Institute
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- A211801
- UG1CA189823 (米国 NIH グラント/契約)
- NCI-2020-11358 (レジストリ識別子：NCI Clinical Trial Reporting Program)
- 2017-002505-35 (EudraCT番号)
- ABCSG 50 (その他の識別子：Austrian Breast & Colorectal Cancer Study Group)
- 2017 (米国 NIH グラント/契約)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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