Denosumabin vaikutuksen tutkiminen rintasyövän ehkäisyssä naisilla, joilla on BRCA1- ituradamutaatio (BRCA-P)
BRCA-P: satunnaistettu, kaksoissokkoutettu, lumekontrolloitu, monikeskus, 3. vaiheen kansainvälinen tutkimus denosumabin ehkäisevän vaikutuksen määrittämiseksi rintasyöpään naisilla, joilla on BRCA1- ituradamutaatio
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.
Tutkimuksen yleiskatsaus
Tila
Interventio / Hoito
Yksityiskohtainen kuvaus
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.
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Vaihe
- Vaihe 3
Yhteystiedot ja paikat
Opiskelupaikat
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California
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Los Angeles, California, Yhdysvallat, 90033
- USC / Norris Comprehensive Cancer Center
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San Francisco, California, Yhdysvallat, 94115
- UCSF Medical Center-Mount Zion
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Colorado
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Aurora, Colorado, Yhdysvallat, 80012
- Rocky Mountain Cancer Centers-Aurora
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Aurora, Colorado, Yhdysvallat, 80045
- UCHealth University of Colorado Hospital
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Boulder, Colorado, Yhdysvallat, 80304
- Rocky Mountain Cancer Centers-Boulder
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Centennial, Colorado, Yhdysvallat, 80112
- Rocky Mountain Cancer Centers - Centennial
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Denver, Colorado, Yhdysvallat, 80218
- Rocky Mountain Cancer Centers-Midtown
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Denver, Colorado, Yhdysvallat, 80220
- Rocky Mountain Cancer Centers-Rose
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Englewood, Colorado, Yhdysvallat, 80113
- Mountain Blue Cancer Care Center - Swedish
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Englewood, Colorado, Yhdysvallat, 80113
- Rocky Mountain Cancer Centers - Swedish
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Littleton, Colorado, Yhdysvallat, 80120
- Rocky Mountain Cancer Centers-Littleton
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Lone Tree, Colorado, Yhdysvallat, 80124
- Rocky Mountain Cancer Centers-Sky Ridge
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District of Columbia
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Washington D.C., District of Columbia, Yhdysvallat, 20007
- MedStar Georgetown University Hospital
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Illinois
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Chicago, Illinois, Yhdysvallat, 60611
- Northwestern University
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Chicago, Illinois, Yhdysvallat, 60637
- University of Chicago Comprehensive Cancer Center
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Evanston, Illinois, Yhdysvallat, 60201
- NorthShore University HealthSystem-Evanston Hospital
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Highland Park, Illinois, Yhdysvallat, 60035
- NorthShore University HealthSystem-Highland Park Hospital
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Urbana, Illinois, Yhdysvallat, 61801
- Carle Cancer Center
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Kansas
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Overland Park, Kansas, Yhdysvallat, 66211
- University of Kansas Hospital-Indian Creek Campus
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Westwood, Kansas, Yhdysvallat, 66205
- University of Kansas Hospital-Westwood Cancer Center
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Maine
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Scarborough, Maine, Yhdysvallat, 04074
- Maine Medical Center- Scarborough Campus
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South Portland, Maine, Yhdysvallat, 04106
- Maine Medical Partners - South Portland
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Maryland
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Baltimore, Maryland, Yhdysvallat, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
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Massachusetts
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Boston, Massachusetts, Yhdysvallat, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, Yhdysvallat, 02215
- Dana-Farber Cancer Institute
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Michigan
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Ann Arbor, Michigan, Yhdysvallat, 48109
- University of Michigan Comprehensive Cancer Center
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Grand Rapids, Michigan, Yhdysvallat, 49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
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Minnesota
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Rochester, Minnesota, Yhdysvallat, 55905
- Mayo Clinic in Rochester
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Saint Paul, Minnesota, Yhdysvallat, 55101
- Regions Hospital
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Nevada
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Las Vegas, Nevada, Yhdysvallat, 89148
- OptumCare Cancer Care at Fort Apache
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New York
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New York, New York, Yhdysvallat, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, Yhdysvallat, 10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
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North Carolina
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Charlotte, North Carolina, Yhdysvallat, 28204
- Novant Health Presbyterian Medical Center
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Greensboro, North Carolina, Yhdysvallat, 27403
- Novant Health Breast Surgery - Greensboro
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Kernersville, North Carolina, Yhdysvallat, 27284
- Novant Health Cancer Institute - Kernersville
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Mount Airy, North Carolina, Yhdysvallat, 27030
- Novant Health Cancer Institute - Mount Airy
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Thomasville, North Carolina, Yhdysvallat, 27360
- Novant Health Cancer Institute - Thomasville
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Winston-Salem, North Carolina, Yhdysvallat, 27103
- Novant Health Forsyth Medical Center
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North Dakota
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Fargo, North Dakota, Yhdysvallat, 58122
- Sanford Roger Maris Cancer Center
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Ohio
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Columbus, Ohio, Yhdysvallat, 43210
- Ohio State University Comprehensive Cancer Center
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Pennsylvania
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Philadelphia, Pennsylvania, Yhdysvallat, 19104
- University of Pennsylvania/Abramson Cancer Center
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Pittsburgh, Pennsylvania, Yhdysvallat, 15232
- University of Pittsburgh Cancer Institute (UPCI)
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Texas
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Dallas, Texas, Yhdysvallat, 75390
- UT Southwestern/Simmons Cancer Center-Dallas
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Houston, Texas, Yhdysvallat, 77030
- M D Anderson Cancer Center
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Utah
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Salt Lake City, Utah, Yhdysvallat, 84112
- Huntsman Cancer Institute/University of Utah
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Vermont
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Burlington, Vermont, Yhdysvallat, 05401
- University of Vermont Medical Center
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Virginia
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Richmond, Virginia, Yhdysvallat, 23298
- Virginia Commonwealth University/Massey Cancer Center
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
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)
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Ennaltaehkäisy
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Kaksinkertainen
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
|
Kokeellinen: 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 |
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Placebo Comparator: Arm B (placebo)
Patients receive placebo SC q6m for up to 5 years in the absence of disease progression. |
Ancillary studies Given SC |
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Time to the occurrence of any breast cancer (invasive or ductal carcinoma in situ [DCIS])
Aikaikkuna: 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
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Time to invasive breast cancer
Aikaikkuna: Up to 5 years post treatment
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Will be compared between the two treatment arms using a stratified Cox proportional hazards regression model. |
Up to 5 years post treatment
|
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Time to invasive triple negative breast cancer
Aikaikkuna: Up to 5 years post treatment
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Will be compared between the two treatment arms using a stratified Cox proportional hazards regression model. |
Up to 5 years post treatment
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Time to ovarian, fallopian and peritoneal cancer (in women who have not undergone prophylactic bilateral salpingo-oophorectomy)
Aikaikkuna: Up to 5 years post treatment
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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
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Time to other (nonbreast or ovarian cancer) malignancies, including those known to be associated with BRCA1 mutations
Aikaikkuna: Up to 5 years post treatment
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Will be compared between the two treatment arms using a stratified Cox proportional hazards regression model. |
Up to 5 years post treatment
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Time to clinical fractures in pre- and postmenopausal women
Aikaikkuna: Up to 5 years post treatment
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Will be compared between the two treatment arms using a stratified Cox proportional hazards regression model. |
Up to 5 years post treatment
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Frequency of breast biopsies
Aikaikkuna: Up to 5 years post treatment
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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
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Frequency of benign breast lesions
Aikaikkuna: Up to 5 years post treatment
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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
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Assess incidence, nature and severity of adverse events (AEs) using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Aikaikkuna: Up to 5 years post treatment
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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
|
Yhteistyökumppanit ja tutkijat
Tutkijat
- Opintojen puheenjohtaja: Judy E. Garber, MD, MPH, Dana-Farber Cancer Institute
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Ensisijainen valmistuminen (Arvioitu)
Opintojen valmistuminen (Arvioitu)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
- Neoplasmat sivustoittain
- Ihosairaudet
- Iho- ja sidekudostaudit
- Neoplasmat
- Rintojen kasvaimet
- Rintojen sairaudet
- Aminohapot, peptidit ja proteiinit
- Proteiinit
- Vasta -aineet, monoklonaalinen, humanisoitu
- Vasta -aineet, monoklonaalinen
- Vasta -aineet
- Immunoglobuliinit
- Immunoproteiinit
- Veriproteiinit
- Seerumin globuliinit
- Globuliinit
- Denosumabi
Muut tutkimustunnusnumerot
- A211801
- UG1CA189823 (Yhdysvaltain NIH-apuraha/sopimus)
- NCI-2020-11358 (Rekisterin tunniste: NCI Clinical Trial Reporting Program)
- 2017-002505-35 (EudraCT-numero)
- ABCSG 50 (Muu tunniste: Austrian Breast & Colorectal Cancer Study Group)
- 2017 (Yhdysvaltain NIH-apuraha/sopimus)
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
Lääke- ja laitetiedot, tutkimusasiakirjat
Tutkii yhdysvaltalaista FDA sääntelemää lääkevalmistetta
Tutkii yhdysvaltalaista FDA sääntelemää laitetuotetta
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