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Studerer effekten av Denosumab på forebygging av brystkreft hos kvinner med en BRCA1-kimlinjemutasjon (BRCA-P)

1. oktober 2026 oppdatert av: Alliance for Clinical Trials in Oncology

BRCA-P: En randomisert, dobbeltblind, placebokontrollert, multisenter, internasjonal fase 3-studie for å bestemme den forebyggende effekten av Denosumab på brystkreft hos kvinner som bærer en BRCA1-kimlinjemutasjon

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.

Studieoversikt

Status

Aktiv, ikke rekrutterende

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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

Intervensjonell

Registrering (Antatt)

300

Fase

  • Fase 3

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

25 år til 55 år (Voksen)

Tar imot friske frivillige

Ja

Kjønn som er kvalifisert for studier

Hunn

Beskrivelse

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)

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Forebygging
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Dobbelt

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Arm A (denosumab)

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

Ancillary studies

Legemiddel: Denosumab

Given SC
Placebo komparator: Arm B (placebo)

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

Ancillary studies

Legemiddel: Placebo

Given SC

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Time to the occurrence of any breast cancer (invasive or ductal carcinoma in situ [DCIS])
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Time to invasive breast cancer
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Alliance for Clinical Trials in Oncology

Samarbeidspartnere

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

Etterforskere

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

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

14. februar 2023

Primær fullføring (Antatt)

1. juli 2027

Studiet fullført (Antatt)

1. desember 2033

Datoer for studieregistrering

Først innsendt

13. januar 2021

Først innsendt som oppfylte QC-kriteriene

13. januar 2021

Først lagt ut (Faktiske)

15. januar 2021

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

5. oktober 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

1. oktober 2026

Sist bekreftet

1. oktober 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • A211801
  • UG1CA189823 (U.S. NIH-stipend/kontrakt)
  • NCI-2020-11358 (Registeridentifikator: NCI Clinical Trial Reporting Program)
  • 2017-002505-35 (EudraCT-nummer)
  • ABCSG 50 (Annen identifikator: Austrian Breast & Colorectal Cancer Study Group)
  • 2017 (U.S. NIH-stipend/kontrakt)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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