Studium účinku denosumabu na prevenci rakoviny prsu u žen s mutací zárodečné linie BRCA1 (BRCA-P)
BRCA-P: Randomizovaná, dvojitě zaslepená, placebem kontrolovaná, multicentrická, mezinárodní studie fáze 3 k určení preventivního účinku denosumabu na rakovinu prsu u žen nesoucích zárodečnou mutaci 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.
Přehled studie
Postavení
Intervence / Léčba
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 3
Kontakty a umístění
Studijní místa
-
-
California
-
Los Angeles, California, Spojené státy, 90033
- USC / Norris Comprehensive Cancer Center
-
San Francisco, California, Spojené státy, 94115
- UCSF Medical Center-Mount Zion
-
-
Colorado
-
Aurora, Colorado, Spojené státy, 80012
- Rocky Mountain Cancer Centers-Aurora
-
Aurora, Colorado, Spojené státy, 80045
- UCHealth University of Colorado Hospital
-
Boulder, Colorado, Spojené státy, 80304
- Rocky Mountain Cancer Centers-Boulder
-
Centennial, Colorado, Spojené státy, 80112
- Rocky Mountain Cancer Centers - Centennial
-
Denver, Colorado, Spojené státy, 80218
- Rocky Mountain Cancer Centers-Midtown
-
Denver, Colorado, Spojené státy, 80220
- Rocky Mountain Cancer Centers-Rose
-
Englewood, Colorado, Spojené státy, 80113
- Mountain Blue Cancer Care Center - Swedish
-
Englewood, Colorado, Spojené státy, 80113
- Rocky Mountain Cancer Centers - Swedish
-
Littleton, Colorado, Spojené státy, 80120
- Rocky Mountain Cancer Centers-Littleton
-
Lone Tree, Colorado, Spojené státy, 80124
- Rocky Mountain Cancer Centers-Sky Ridge
-
-
District of Columbia
-
Washington D.C., District of Columbia, Spojené státy, 20007
- MedStar Georgetown University Hospital
-
-
Illinois
-
Chicago, Illinois, Spojené státy, 60611
- Northwestern University
-
Chicago, Illinois, Spojené státy, 60637
- University of Chicago Comprehensive Cancer Center
-
Evanston, Illinois, Spojené státy, 60201
- NorthShore University HealthSystem-Evanston Hospital
-
Highland Park, Illinois, Spojené státy, 60035
- NorthShore University HealthSystem-Highland Park Hospital
-
Urbana, Illinois, Spojené státy, 61801
- Carle Cancer Center
-
-
Kansas
-
Overland Park, Kansas, Spojené státy, 66211
- University of Kansas Hospital-Indian Creek Campus
-
Westwood, Kansas, Spojené státy, 66205
- University of Kansas Hospital-Westwood Cancer Center
-
-
Maine
-
Scarborough, Maine, Spojené státy, 04074
- Maine Medical Center- Scarborough Campus
-
South Portland, Maine, Spojené státy, 04106
- Maine Medical Partners - South Portland
-
-
Maryland
-
Baltimore, Maryland, Spojené státy, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
-
-
Massachusetts
-
Boston, Massachusetts, Spojené státy, 02215
- Beth Israel Deaconess Medical Center
-
Boston, Massachusetts, Spojené státy, 02215
- Dana-Farber Cancer Institute
-
-
Michigan
-
Ann Arbor, Michigan, Spojené státy, 48109
- University of Michigan Comprehensive Cancer Center
-
Grand Rapids, Michigan, Spojené státy, 49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
-
-
Minnesota
-
Rochester, Minnesota, Spojené státy, 55905
- Mayo Clinic in Rochester
-
Saint Paul, Minnesota, Spojené státy, 55101
- Regions Hospital
-
-
Nevada
-
Las Vegas, Nevada, Spojené státy, 89148
- OptumCare Cancer Care at Fort Apache
-
-
New York
-
New York, New York, Spojené státy, 10065
- Memorial Sloan Kettering Cancer Center
-
New York, New York, Spojené státy, 10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
-
-
North Carolina
-
Charlotte, North Carolina, Spojené státy, 28204
- Novant Health Presbyterian Medical Center
-
Greensboro, North Carolina, Spojené státy, 27403
- Novant Health Breast Surgery - Greensboro
-
Kernersville, North Carolina, Spojené státy, 27284
- Novant Health Cancer Institute - Kernersville
-
Mount Airy, North Carolina, Spojené státy, 27030
- Novant Health Cancer Institute - Mount Airy
-
Thomasville, North Carolina, Spojené státy, 27360
- Novant Health Cancer Institute - Thomasville
-
Winston-Salem, North Carolina, Spojené státy, 27103
- Novant Health Forsyth Medical Center
-
-
North Dakota
-
Fargo, North Dakota, Spojené státy, 58122
- Sanford Roger Maris Cancer Center
-
-
Ohio
-
Columbus, Ohio, Spojené státy, 43210
- Ohio State University Comprehensive Cancer Center
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, Spojené státy, 19104
- University of Pennsylvania/Abramson Cancer Center
-
Pittsburgh, Pennsylvania, Spojené státy, 15232
- University of Pittsburgh Cancer Institute (UPCI)
-
-
Texas
-
Dallas, Texas, Spojené státy, 75390
- UT Southwestern/Simmons Cancer Center-Dallas
-
Houston, Texas, Spojené státy, 77030
- M D Anderson Cancer Center
-
-
Utah
-
Salt Lake City, Utah, Spojené státy, 84112
- Huntsman Cancer Institute/University of Utah
-
-
Vermont
-
Burlington, Vermont, Spojené státy, 05401
- University of Vermont Medical Center
-
-
Virginia
-
Richmond, Virginia, Spojené státy, 23298
- Virginia Commonwealth University/Massey Cancer Center
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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)
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Prevence
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: 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 |
|
Komparátor placeba: Arm B (placebo)
Patients receive placebo SC q6m for up to 5 years in the absence of disease progression. |
Ancillary studies Given SC |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Time to the occurrence of any breast cancer (invasive or ductal carcinoma in situ [DCIS])
Časové okno: 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
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Time to invasive breast cancer
Časové okno: 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
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
|
Spolupracovníci a vyšetřovatelé
Vyšetřovatelé
- Studijní židle: Judy E. Garber, MD, MPH, Dana-Farber Cancer Institute
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Novotvary podle místa
- Kožní choroby
- Onemocnění kůže a pojivové tkáně
- Novotvary
- Novotvary prsu
- Nemoci prsu
- Aminokyseliny, peptidy a proteiny
- Proteiny
- Protilátky, monoklonální, humanizované
- Protilátky, monoklonální
- Protilátky
- Imunoglobuliny
- Imunoproteiny
- Krevní proteiny
- Sérové globuliny
- Globuliny
- Denosumab
Další identifikační čísla studie
- A211801
- UG1CA189823 (Grant/smlouva NIH USA)
- NCI-2020-11358 (Identifikátor registru: NCI Clinical Trial Reporting Program)
- 2017-002505-35 (Číslo EudraCT)
- ABCSG 50 (Jiný identifikátor: Austrian Breast & Colorectal Cancer Study Group)
- 2017 (Grant/smlouva NIH USA)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .