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Estudio del efecto de denosumab en la prevención del cáncer de mama en mujeres con una mutación de línea germinal BRCA1 (BRCA-P)

1 de octubre de 2026 actualizado por: Alliance for Clinical Trials in Oncology

BRCA-P: un estudio internacional de fase 3, aleatorizado, doble ciego, controlado con placebo, multicéntrico, para determinar el efecto preventivo de denosumab sobre el cáncer de mama en mujeres portadoras de una mutación de la línea germinal BRCA1

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.

Descripción general del estudio

Estado

Activo, no reclutando

Condiciones

Intervención / Tratamiento

Descripción detallada

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.

Tipo de estudio

Intervencionista

Inscripción (Estimado)

300

Fase

  • Fase 3

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

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

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

25 años a 55 años (Adulto)

Acepta Voluntarios Saludables

Sí

Géneros elegibles para el estudio

Femenino

Descripción

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)

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Prevención
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Doble

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Arm A (denosumab)

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

Ancillary studies

Droga: Denosumab

Given SC
Comparador de placebos: Arm B (placebo)

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

Ancillary studies

Droga: Placebo

Given SC

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Time to the occurrence of any breast cancer (invasive or ductal carcinoma in situ [DCIS])
Periodo de tiempo: 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

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Time to invasive breast cancer
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Alliance for Clinical Trials in Oncology

Colaboradores

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

Investigadores

  • Silla de estudio: Judy E. Garber, MD, MPH, Dana-Farber Cancer Institute

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

14 de febrero de 2023

Finalización primaria (Estimado)

1 de julio de 2027

Finalización del estudio (Estimado)

1 de diciembre de 2033

Fechas de registro del estudio

Enviado por primera vez

13 de enero de 2021

Primero enviado que cumplió con los criterios de control de calidad

13 de enero de 2021

Publicado por primera vez (Actual)

15 de enero de 2021

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

5 de octubre de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

1 de octubre de 2026

Última verificación

1 de octubre de 2026

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • A211801
  • UG1CA189823 (Subvención/contrato del NIH de EE. UU.)
  • NCI-2020-11358 (Identificador de registro: NCI Clinical Trial Reporting Program)
  • 2017-002505-35 (Número EudraCT)
  • ABCSG 50 (Otro identificador: Austrian Breast & Colorectal Cancer Study Group)
  • 2017 (Subvención/contrato del NIH de EE. UU.)

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

SÍ

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

Sí

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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