Studera effekten av Denosumab på att förebygga bröstcancer hos kvinnor med en BRCA1 könslinjemutation (BRCA-P)
BRCA-P: En randomiserad, dubbelblind, placebokontrollerad, multicenter, internationell fas 3-studie för att fastställa den förebyggande effekten av Denosumab på bröstcancer hos kvinnor som bär på en BRCA1 könscellsmutation
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.
Studieöversikt
Status
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Inskrivning (Beräknad)
Fas
- Fas 3
Kontakter och platser
Studieorter
-
-
California
-
Los Angeles, California, Förenta staterna, 90033
- USC / Norris Comprehensive Cancer Center
-
San Francisco, California, Förenta staterna, 94115
- UCSF Medical Center-Mount Zion
-
-
Colorado
-
Aurora, Colorado, Förenta staterna, 80012
- Rocky Mountain Cancer Centers-Aurora
-
Aurora, Colorado, Förenta staterna, 80045
- UCHealth University of Colorado Hospital
-
Boulder, Colorado, Förenta staterna, 80304
- Rocky Mountain Cancer Centers-Boulder
-
Centennial, Colorado, Förenta staterna, 80112
- Rocky Mountain Cancer Centers - Centennial
-
Denver, Colorado, Förenta staterna, 80218
- Rocky Mountain Cancer Centers-Midtown
-
Denver, Colorado, Förenta staterna, 80220
- Rocky Mountain Cancer Centers-Rose
-
Englewood, Colorado, Förenta staterna, 80113
- Mountain Blue Cancer Care Center - Swedish
-
Englewood, Colorado, Förenta staterna, 80113
- Rocky Mountain Cancer Centers - Swedish
-
Littleton, Colorado, Förenta staterna, 80120
- Rocky Mountain Cancer Centers-Littleton
-
Lone Tree, Colorado, Förenta staterna, 80124
- Rocky Mountain Cancer Centers-Sky Ridge
-
-
District of Columbia
-
Washington D.C., District of Columbia, Förenta staterna, 20007
- MedStar Georgetown University Hospital
-
-
Illinois
-
Chicago, Illinois, Förenta staterna, 60611
- Northwestern University
-
Chicago, Illinois, Förenta staterna, 60637
- University of Chicago Comprehensive Cancer Center
-
Evanston, Illinois, Förenta staterna, 60201
- NorthShore University HealthSystem-Evanston Hospital
-
Highland Park, Illinois, Förenta staterna, 60035
- NorthShore University HealthSystem-Highland Park Hospital
-
Urbana, Illinois, Förenta staterna, 61801
- Carle Cancer Center
-
-
Kansas
-
Overland Park, Kansas, Förenta staterna, 66211
- University of Kansas Hospital-Indian Creek Campus
-
Westwood, Kansas, Förenta staterna, 66205
- University of Kansas Hospital-Westwood Cancer Center
-
-
Maine
-
Scarborough, Maine, Förenta staterna, 04074
- Maine Medical Center- Scarborough Campus
-
South Portland, Maine, Förenta staterna, 04106
- Maine Medical Partners - South Portland
-
-
Maryland
-
Baltimore, Maryland, Förenta staterna, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
-
-
Massachusetts
-
Boston, Massachusetts, Förenta staterna, 02215
- Beth Israel Deaconess Medical Center
-
Boston, Massachusetts, Förenta staterna, 02215
- Dana-Farber Cancer Institute
-
-
Michigan
-
Ann Arbor, Michigan, Förenta staterna, 48109
- University of Michigan Comprehensive Cancer Center
-
Grand Rapids, Michigan, Förenta staterna, 49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
-
-
Minnesota
-
Rochester, Minnesota, Förenta staterna, 55905
- Mayo Clinic in Rochester
-
Saint Paul, Minnesota, Förenta staterna, 55101
- Regions Hospital
-
-
Nevada
-
Las Vegas, Nevada, Förenta staterna, 89148
- OptumCare Cancer Care at Fort Apache
-
-
New York
-
New York, New York, Förenta staterna, 10065
- Memorial Sloan Kettering Cancer Center
-
New York, New York, Förenta staterna, 10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
-
-
North Carolina
-
Charlotte, North Carolina, Förenta staterna, 28204
- Novant Health Presbyterian Medical Center
-
Greensboro, North Carolina, Förenta staterna, 27403
- Novant Health Breast Surgery - Greensboro
-
Kernersville, North Carolina, Förenta staterna, 27284
- Novant Health Cancer Institute - Kernersville
-
Mount Airy, North Carolina, Förenta staterna, 27030
- Novant Health Cancer Institute - Mount Airy
-
Thomasville, North Carolina, Förenta staterna, 27360
- Novant Health Cancer Institute - Thomasville
-
Winston-Salem, North Carolina, Förenta staterna, 27103
- Novant Health Forsyth Medical Center
-
-
North Dakota
-
Fargo, North Dakota, Förenta staterna, 58122
- Sanford Roger Maris Cancer Center
-
-
Ohio
-
Columbus, Ohio, Förenta staterna, 43210
- Ohio State University Comprehensive Cancer Center
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, Förenta staterna, 19104
- University of Pennsylvania/Abramson Cancer Center
-
Pittsburgh, Pennsylvania, Förenta staterna, 15232
- University of Pittsburgh Cancer Institute (UPCI)
-
-
Texas
-
Dallas, Texas, Förenta staterna, 75390
- UT Southwestern/Simmons Cancer Center-Dallas
-
Houston, Texas, Förenta staterna, 77030
- M D Anderson Cancer Center
-
-
Utah
-
Salt Lake City, Utah, Förenta staterna, 84112
- Huntsman Cancer Institute/University of Utah
-
-
Vermont
-
Burlington, Vermont, Förenta staterna, 05401
- University of Vermont Medical Center
-
-
Virginia
-
Richmond, Virginia, Förenta staterna, 23298
- Virginia Commonwealth University/Massey Cancer Center
-
-
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
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
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Förebyggande
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Dubbel
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: 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 |
|
Placebo-jämförare: Arm B (placebo)
Patients receive placebo SC q6m for up to 5 years in the absence of disease progression. |
Ancillary studies Given SC |
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Time to the occurrence of any breast cancer (invasive or ductal carcinoma in situ [DCIS])
Tidsram: 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
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Time to invasive breast cancer
Tidsram: 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
Tidsram: 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)
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
|
Samarbetspartners och utredare
Utredare
- Studiestol: Judy E. Garber, MD, MPH, Dana-Farber Cancer Institute
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Beräknad)
Avslutad studie (Beräknad)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Faktisk)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Neoplasmer efter plats
- Hudsjukdomar
- Hud- och bindvävssjukdomar
- Neoplasmer
- Bröstneoplasmer
- Bröstsjukdomar
- Aminosyror, peptider och proteiner
- Proteiner
- Antikroppar, monoklonal, humaniserad
- Antikroppar, monoklonal
- Antikroppar
- Immunglobuliner
- Immunoproteiner
- Blodproteiner
- Serumglobuliner
- Globuliner
- Denosumab
Andra studie-ID-nummer
- A211801
- UG1CA189823 (U.S.S. NIH-anslag/kontrakt)
- NCI-2020-11358 (Registeridentifierare: NCI Clinical Trial Reporting Program)
- 2017-002505-35 (EudraCT-nummer)
- ABCSG 50 (Annan identifierare: Austrian Breast & Colorectal Cancer Study Group)
- 2017 (U.S.S. NIH-anslag/kontrakt)
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
Läkemedels- och apparatinformation, studiedokument
Studerar en amerikansk FDA-reglerad läkemedelsprodukt
Studerar en amerikansk FDA-reglerad produktprodukt
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .