Studio dell'effetto di Denosumab sulla prevenzione del cancro al seno nelle donne con una mutazione della linea germinale BRCA1 (BRCA-P)
BRCA-P: uno studio internazionale di fase 3 randomizzato, in doppio cieco, controllato con placebo, multicentrico per determinare l'effetto preventivo di Denosumab sul carcinoma mammario nelle donne portatrici di una mutazione della linea germinale 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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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 di studio
Iscrizione (Stimato)
Fase
- Fase 3
Contatti e Sedi
Luoghi di studio
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California
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Los Angeles, California, Stati Uniti, 90033
- USC / Norris Comprehensive Cancer Center
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San Francisco, California, Stati Uniti, 94115
- UCSF Medical Center-Mount Zion
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Colorado
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Aurora, Colorado, Stati Uniti, 80012
- Rocky Mountain Cancer Centers-Aurora
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Aurora, Colorado, Stati Uniti, 80045
- UCHealth University of Colorado Hospital
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Boulder, Colorado, Stati Uniti, 80304
- Rocky Mountain Cancer Centers-Boulder
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Centennial, Colorado, Stati Uniti, 80112
- Rocky Mountain Cancer Centers - Centennial
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Denver, Colorado, Stati Uniti, 80218
- Rocky Mountain Cancer Centers-Midtown
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Denver, Colorado, Stati Uniti, 80220
- Rocky Mountain Cancer Centers-Rose
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Englewood, Colorado, Stati Uniti, 80113
- Mountain Blue Cancer Care Center - Swedish
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Englewood, Colorado, Stati Uniti, 80113
- Rocky Mountain Cancer Centers - Swedish
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Littleton, Colorado, Stati Uniti, 80120
- Rocky Mountain Cancer Centers-Littleton
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Lone Tree, Colorado, Stati Uniti, 80124
- Rocky Mountain Cancer Centers-Sky Ridge
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District of Columbia
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Washington D.C., District of Columbia, Stati Uniti, 20007
- MedStar Georgetown University Hospital
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Illinois
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Chicago, Illinois, Stati Uniti, 60611
- Northwestern University
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Chicago, Illinois, Stati Uniti, 60637
- University of Chicago Comprehensive Cancer Center
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Evanston, Illinois, Stati Uniti, 60201
- NorthShore University HealthSystem-Evanston Hospital
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Highland Park, Illinois, Stati Uniti, 60035
- NorthShore University HealthSystem-Highland Park Hospital
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Urbana, Illinois, Stati Uniti, 61801
- Carle Cancer Center
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Kansas
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Overland Park, Kansas, Stati Uniti, 66211
- University of Kansas Hospital-Indian Creek Campus
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Westwood, Kansas, Stati Uniti, 66205
- University of Kansas Hospital-Westwood Cancer Center
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Maine
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Scarborough, Maine, Stati Uniti, 04074
- Maine Medical Center- Scarborough Campus
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South Portland, Maine, Stati Uniti, 04106
- Maine Medical Partners - South Portland
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Maryland
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Baltimore, Maryland, Stati Uniti, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
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Massachusetts
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Boston, Massachusetts, Stati Uniti, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, Stati Uniti, 02215
- Dana-Farber Cancer Institute
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Michigan
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Ann Arbor, Michigan, Stati Uniti, 48109
- University of Michigan Comprehensive Cancer Center
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Grand Rapids, Michigan, Stati Uniti, 49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
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Minnesota
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Rochester, Minnesota, Stati Uniti, 55905
- Mayo Clinic in Rochester
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Saint Paul, Minnesota, Stati Uniti, 55101
- Regions Hospital
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Nevada
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Las Vegas, Nevada, Stati Uniti, 89148
- OptumCare Cancer Care at Fort Apache
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New York
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New York, New York, Stati Uniti, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, Stati Uniti, 10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
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North Carolina
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Charlotte, North Carolina, Stati Uniti, 28204
- Novant Health Presbyterian Medical Center
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Greensboro, North Carolina, Stati Uniti, 27403
- Novant Health Breast Surgery - Greensboro
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Kernersville, North Carolina, Stati Uniti, 27284
- Novant Health Cancer Institute - Kernersville
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Mount Airy, North Carolina, Stati Uniti, 27030
- Novant Health Cancer Institute - Mount Airy
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Thomasville, North Carolina, Stati Uniti, 27360
- Novant Health Cancer Institute - Thomasville
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Winston-Salem, North Carolina, Stati Uniti, 27103
- Novant Health Forsyth Medical Center
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North Dakota
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Fargo, North Dakota, Stati Uniti, 58122
- Sanford Roger Maris Cancer Center
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Ohio
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Columbus, Ohio, Stati Uniti, 43210
- Ohio State University Comprehensive Cancer Center
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Pennsylvania
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Philadelphia, Pennsylvania, Stati Uniti, 19104
- University of Pennsylvania/Abramson Cancer Center
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Pittsburgh, Pennsylvania, Stati Uniti, 15232
- University of Pittsburgh Cancer Institute (UPCI)
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Texas
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Dallas, Texas, Stati Uniti, 75390
- UT Southwestern/Simmons Cancer Center-Dallas
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Houston, Texas, Stati Uniti, 77030
- M D Anderson Cancer Center
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Utah
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Salt Lake City, Utah, Stati Uniti, 84112
- Huntsman Cancer Institute/University of Utah
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Vermont
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Burlington, Vermont, Stati Uniti, 05401
- University of Vermont Medical Center
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Virginia
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Richmond, Virginia, Stati Uniti, 23298
- Virginia Commonwealth University/Massey Cancer Center
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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)
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Prevenzione
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Doppio
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: 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 |
|
Comparatore placebo: Arm B (placebo)
Patients receive placebo SC q6m for up to 5 years in the absence of disease progression. |
Ancillary studies Given SC |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Time to the occurrence of any breast cancer (invasive or ductal carcinoma in situ [DCIS])
Lasso di tempo: 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
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Time to invasive breast cancer
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
|
Collaboratori e investigatori
Investigatori
- Cattedra di studio: Judy E. Garber, MD, MPH, Dana-Farber Cancer Institute
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Stimato)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Neoplasie per sede
- Malattie della pelle
- Malattie della pelle e del tessuto connettivo
- Neoplasie
- Neoplasie mammarie
- Malattie del seno
- Aminoacidi, peptidi e proteine
- Proteine
- Anticorpi, monoclonali, umanizzati
- Anticorpi, monoclonali
- Anticorpi
- Immunoglobuline
- Immunoproteine
- Proteine del sangue
- Globuline sieriche
- Globuline
- Denosumab
Altri numeri di identificazione dello studio
- A211801
- UG1CA189823 (Sovvenzione/contratto NIH degli Stati Uniti)
- NCI-2020-11358 (Identificatore di registro: NCI Clinical Trial Reporting Program)
- 2017-002505-35 (Numero EudraCT)
- ABCSG 50 (Altro identificatore: Austrian Breast & Colorectal Cancer Study Group)
- 2017 (Sovvenzione/contratto NIH degli Stati Uniti)
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Informazioni su farmaci e dispositivi, documenti di studio
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