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Het bestuderen van het effect van Denosumab op het voorkomen van borstkanker bij vrouwen met een BRCA1-kiembaanmutatie (BRCA-P)

1 oktober 2026 bijgewerkt door: Alliance for Clinical Trials in Oncology

BRCA-P: een gerandomiseerde, dubbelblinde, placebogecontroleerde, multicenter, internationale fase 3-studie om het preventieve effect van denosumab op borstkanker te bepalen bij vrouwen die drager zijn van een BRCA1-kiembaanmutatie

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.

Studie Overzicht

Toestand

Actief, niet wervend

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Geschat)

300

Fase

  • Fase 3

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

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

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

25 jaar tot 55 jaar (Volwassen)

Accepteert gezonde vrijwilligers

Ja

Geslachten die in aanmerking komen voor studie

Vrouw

Beschrijving

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)

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Preventie
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Dubbele

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Arm A (denosumab)

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

Ancillary studies

Geneesmiddel: Denosumab

Given SC
Placebo-vergelijker: Arm B (placebo)

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

Ancillary studies

Geneesmiddel: Placebo

Given SC

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Time to the occurrence of any breast cancer (invasive or ductal carcinoma in situ [DCIS])
Tijdsspanne: 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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Time to invasive breast cancer
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Alliance for Clinical Trials in Oncology

Medewerkers

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

Onderzoekers

  • Studie stoel: Judy E. Garber, MD, MPH, Dana-Farber Cancer Institute

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

14 februari 2023

Primaire voltooiing (Geschat)

1 juli 2027

Studie voltooiing (Geschat)

1 december 2033

Studieregistratiedata

Eerst ingediend

13 januari 2021

Eerst ingediend dat voldeed aan de QC-criteria

13 januari 2021

Eerst geplaatst (Werkelijk)

15 januari 2021

Updates van studierecords

Laatste update geplaatst (Werkelijk)

5 oktober 2026

Laatste update ingediend die voldeed aan QC-criteria

1 oktober 2026

Laatst geverifieerd

1 oktober 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • A211801
  • UG1CA189823 (Subsidie/contract van de Amerikaanse NIH)
  • NCI-2020-11358 (Register-ID: NCI Clinical Trial Reporting Program)
  • 2017-002505-35 (EudraCT-nummer)
  • ABCSG 50 (Andere identificatie: Austrian Breast & Colorectal Cancer Study Group)
  • 2017 (Subsidie/contract van de Amerikaanse NIH)

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

JA

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Ja

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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