Study of Denosumab as Adjuvant Treatment for Women With High Risk Early Breast Cancer Receiving Neoadjuvant or Adjuvant Therapy (D-CARE)

Breast Cancer Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase 3 Study of Denosumab as Adjuvant Treatment for Women With Early-Stage Breast Cancer at High Risk of Recurrence (D-CARE)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01077154
• Other study ID #: 20060359
• Secondary ID: 2009-011299-32
• Status: Terminated
• Phase: Phase 3
• Start date: June 2, 2010
• Est. completion date: March 26, 2018

Study information

• Verified date: September 2021
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase 3 trial is studying the effect of denosumab to see if it can prevent disease recurrence in the bone or in any other part of the body, when it is given as adjuvant therapy for women with early-stage breast cancer, who are at high risk of disease recurrence.

Description:

Eligible participants were randomized in a 1:1 ratio to receive denosumab 120 mg or placebo subcutaneously (SC) for up to 5 years. Randomization was stratified based on:

1. Breast cancer therapy/lymph node (LN) status: neoadjuvant therapy/any LN status versus adjuvant therapy/LN negative (based on axillary LN dissection, or based on sentinel node status) versus adjuvant therapy/LN positive

2. Hormone receptor (estrogen receptor [ER]/progesterone receptor [PR]) status: ER and/or PR positive versus ER and PR negative

3. Human epidermal growth factor receptor 2 (HER-2) status: HER-2 positive versus HER-2 negative

4. Age: < 50 years versus ≥ 50 years

5. Geographic Region: Japan versus Other regions.

The primary analysis was conducted after all enrolled participants had the opportunity to complete 5 years of treatment from study day 1.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4509
• Est. completion date: March 26, 2018
• Est. primary completion date: August 31, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed, American Joint Committee on Cancer (AJCC) stage II or III breast cancer

• High risk of breast cancer recurrence, defined as documented evidence of one or more of the following criteria:

i) Biopsy evidence of breast cancer in regional lymph node(s) (LN) (node-positive disease); Nodal micrometastases only are not considered node positive ii) Tumor size > 5 cm (T3) or locally advanced disease (T4)

• Documented pathological evaluation of the breast cancer for hormone receptor (estrogen receptor [ER] and progesterone receptor [PR]) status and HER-2 status

• Subjects must be receiving or be scheduled to receive standard of care systemic adjuvant or neoadjuvant chemotherapy and/or endocrine therapy and/or HER-2 targeted therapy

• For subjects receiving adjuvant therapy only:

• subjects must have undergone complete resection of the primary tumor with clean surgical margins, or subjects must have undergone resection of the primary tumor and be scheduled for further treatment of the primary tumor with curative intent. Definitive treatment must be planned to be completed within approximately 9 months of randomization

• Time between definitive surgery and randomization must be = 12 weeks. Definitive surgery may include secondary interventions (e.g. to clear inadequate surgical margins)

• Subjects with node positive disease must have undergone treatment of axillary LN with curative intent, or subjects must be scheduled for further treatment of regional lymph nodes with curative intent. Definitive treatment must be planned to be completed within approximately 9 months of randomization

• Subjects must not have received prior neoadjuvant treatment. Endocrine treatment for less than 30 days prior to surgery is not considered prior neoadjuvant treatment

• For subjects receiving neoadjuvant therapy only:

• Time between start of neoadjuvant treatment and randomization must be = 8 weeks and subjects must be scheduled to undergo definitive treatment (including surgery and/or radiotherapy) with curative intent within approximately 9 months of starting neoadjuvant treatment

• Female subjects with age = 18 years

• Subjects with reproductive potential must have a negative pregnancy test within 14 days before randomization

• Serum calcium or albumin-adjusted serum calcium = 2.0 mmol/L (8.0 mg/dL) and = 2.9 mmol/L (11.5 mg/dL)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Written informed consent before any study-specific procedure is performed

Exclusion Criteria:

• Prior or current evidence of any metastatic involvement of any distant site

• History of breast cancer (other than ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS]) prior to the current diagnosis

• Osteoporosis requiring treatment at the time of randomization or treatment considered likely to become necessary within the subsequent six months

• Any prior or synchronous malignancy (other than breast cancer), except i) Malignancy treated with curative intent and with no evidence of disease for = 5 years prior to enrollment and considered to be at low risk for recurrence by the treating physician ii) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease

• Active infection with Hepatitis B virus or Hepatitis C virus

• Known infection with human immunodeficiency virus (HIV)

• Prior history or current evidence of osteomyelitis/osteonecrosis of the jaw

• Active dental or jaw condition which requires oral surgery

• Planned invasive dental procedure for the course of the study

• Non-healed dental or oral surgery

• Use of oral bisphosphonates within the past 1 year

• Prior or current IV bisphosphonate administration

• Prior administration of denosumab

• Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or investigational drug study(s), or subject is receiving other investigational agent(s)

• Subject is pregnant or breast feeding, or planning to become pregnant within 7 months after the end of treatment.

• Subject is of child bearing potential and is not willing to use, in combination with her partner, 2 highly effective methods of contraception or abstinence during treatment and for 5 months after the end of treatment

• Subject has known sensitivity to any of the products to be administered during the study (e.g., mammalian derived products, calcium, or vitamin D)

• Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.

• Any major medical or psychiatric disorder that in the opinion of the investigator prevent the subject from completing the study or interfere with the interpretation of the study results

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Placebo
Administered subcutaneously for up to 5 years
• Denosumab
Administered subcutaneously for up to 5 years

Locations

Country	Name	City	State
Argentina	Research Site	Neuquen	Neuquén
Argentina	Research Site	Provincia De Santa Fe	Santa Fe
Argentina	Research Site	Quilmes	Buenos Aires
Argentina	Research Site	Quilmes	Buenos Aires
Argentina	Research Site	San Martin	Buenos Aires
Argentina	Research Site	San Miguel de Tucuman	Tucuman
Australia	Research Site	Bedford Park	South Australia
Australia	Research Site	Bentleigh East	Victoria
Australia	Research Site	Camperdown	New South Wales
Australia	Research Site	Caringbah	New South Wales
Australia	Research Site	East Melbourne	Victoria
Australia	Research Site	Fitzroy	Victoria
Australia	Research Site	Footscray	Victoria
Australia	Research Site	Frankston	Victoria
Australia	Research Site	Heidelberg	Victoria
Australia	Research Site	Kogarah	New South Wales
Australia	Research Site	Malvern	Victoria
Australia	Research Site	Parkville	Victoria
Australia	Research Site	Perth	Western Australia
Australia	Research Site	Richmond	Victoria
Australia	Research Site	Ringwood East	Victoria
Australia	Research Site	Subiaco	Western Australia
Australia	Research Site	Tweed Heads	New South Wales
Australia	Research Site	Wahroonga	New South Wales
Australia	Research Site	Warrnambool	Victoria
Australia	Research Site	Wodonga	Victoria
Belgium	Research Site	Antwerpen
Belgium	Research Site	Bonheiden
Belgium	Research Site	Brugge
Belgium	Research Site	Brussel
Belgium	Research Site	Bruxelles
Belgium	Research Site	Bruxelles
Belgium	Research Site	Edegem
Belgium	Research Site	Gent
Belgium	Research Site	Hasselt
Belgium	Research Site	Kortrijk
Belgium	Research Site	Leuven
Belgium	Research Site	Liège
Belgium	Research Site	Libramont
Belgium	Research Site	Namur
Belgium	Research Site	Oostende
Belgium	Research Site	Ottignies
Belgium	Research Site	Sint-Niklaas
Belgium	Research Site	Tournai
Belgium	Research Site	Wilrijk
Belgium	Research Site	Yvoir
Brazil	Research Site	Barretos	São Paulo
Brazil	Research Site	Curitiba	Paraná
Brazil	Research Site	ItajaÃ-	Santa Catarina
Brazil	Research Site	Londrina	Paraná
Brazil	Research Site	Porto Alegre	Rio Grande Do Sul
Brazil	Research Site	Porto Alegre	Rio Grande Do Sul
Brazil	Research Site	Porto Alegre	Rio Grande Do Sul
Brazil	Research Site	São Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	Salvador	Bahia
Brazil	Research Site	Salvador	Bahia
Brazil	Research Site	Santo Andre	São Paulo
Brazil	Research Site	Sao Paulo	São Paulo
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Rousse
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Stara Zagora
Bulgaria	Research Site	Varna
Bulgaria	Research Site	Veliko Tarnovo
Canada	Research Site	Barrie	Ontario
Canada	Research Site	Brampton	Ontario
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Greenfield Park	Quebec
Canada	Research Site	Kelowna	British Columbia
Canada	Research Site	Kingston	Ontario
Canada	Research Site	Kitchener	Ontario
Canada	Research Site	Moncton	New Brunswick
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Sault Ste. Marie	Ontario
Canada	Research Site	Sherbrooke	Quebec
Canada	Research Site	St. John's	Newfoundland and Labrador
Canada	Research Site	Sudbury	Ontario
Canada	Research Site	Sydney	Nova Scotia
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Victoria	British Columbia
Chile	Research Site	Santiago
Chile	Research Site	Temuco	CautÃ-n
Chile	Research Site	Vina del Mar	ValparaÃ-so
Czechia	Research Site	Brno
Czechia	Research Site	Brno
Czechia	Research Site	Chomutov
Czechia	Research Site	Horovice
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Olomouc
Czechia	Research Site	Praha 10
Czechia	Research Site	Praha 10
Czechia	Research Site	Praha 4
Czechia	Research Site	Praha 5
Czechia	Research Site	Praha 8
Denmark	Research Site	Ã…rhus C
Denmark	Research Site	Herning
Denmark	Research Site	Vejle
Denmark	Research Site	Viborg
France	Research Site	Angers
France	Research Site	Bordeaux Cedex
France	Research Site	Dijon
France	Research Site	Grenoble
France	Research Site	Hyères
France	Research Site	Le Mans
France	Research Site	Lille
France	Research Site	Monaco
France	Research Site	Nantes Cedex 2
France	Research Site	Paris
France	Research Site	Pierre-Benite
France	Research Site	Saint Priest en Jarez Cedex
France	Research Site	Strasbourg cedex
France	Research Site	Villejuif cedex
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Bonn
Germany	Research Site	Bottrop
Germany	Research Site	Erlangen
Germany	Research Site	Frankfurt
Germany	Research Site	Kiel
Germany	Research Site	Koblenz
Germany	Research Site	München
Germany	Research Site	München
Germany	Research Site	München
Germany	Research Site	Mannheim
Germany	Research Site	Recklinghausen
Germany	Research Site	Rostock
Germany	Research Site	Tübingen
Germany	Research Site	Trier
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Heraklion
Greece	Research Site	Patra
Greece	Research Site	Thessaloniki
Greece	Research Site	Thessaloniki
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	New Territories
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Gyor
Hungary	Research Site	Nyiregyhaza
Hungary	Research Site	Pecs
Hungary	Research Site	Szeged
Hungary	Research Site	Szekesfehervar
Hungary	Research Site	Szolnok
Hungary	Research Site	Zalaegerszeg
India	Research Site	Ahmednagar	Maharashtra
India	Research Site	Aurangabad	Maharashtra
India	Research Site	Bangalore	Karnataka
India	Research Site	Chennai	Tamil Nadu
India	Research Site	Hyderabad	Andhra Pradesh
India	Research Site	Jaipur	Rajasthan
India	Research Site	Madurai	Tamil Nadu
India	Research Site	Miraj	Maharashtra
India	Research Site	Mumbai	Maharashtra
India	Research Site	Mumbai	Maharashtra
India	Research Site	Nashik	Maharashtra
India	Research Site	Nashik	Maharashtra
India	Research Site	Pune	Maharashtra
Ireland	Research Site	Cork
Ireland	Research Site	Dublin
Ireland	Research Site	Dublin
Ireland	Research Site	Dublin
Ireland	Research Site	Limerick
Ireland	Research Site	Waterford
Israel	Research Site	Ashkelon
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Kfar Sava
Israel	Research Site	Petah Tikva
Israel	Research Site	Poria Eylit
Israel	Research Site	Rehovot
Israel	Research Site	Tel Aviv
Israel	Research Site	Tel Aviv
Italy	Research Site	Ancona
Italy	Research Site	Bari
Italy	Research Site	Brescia
Italy	Research Site	Meldola FC
Italy	Research Site	Milano
Italy	Research Site	Monza (MB)
Italy	Research Site	Palermo
Italy	Research Site	Parma
Italy	Research Site	San Giovanni Rotondo FG
Italy	Research Site	Treviglio (BG)
Italy	Research Site	Varese
Japan	Research Site	Akashi-shi	Hyogo
Japan	Research Site	Chuo-ku	Tokyo
Japan	Research Site	Fukuoka-shi	Fukuoka
Japan	Research Site	Hidaka-Shi	Saitama
Japan	Research Site	Isehara-shi	Kanagawa
Japan	Research Site	Kagoshima-shi	Kagoshima
Japan	Research Site	Kitaadachi-gun	Saitama
Japan	Research Site	Kitakyushu-shi	Fukuoka
Japan	Research Site	Kumamoto-shi	Kumamoto
Japan	Research Site	Kurashiki-shi	Okayama
Japan	Research Site	Kure-shi	Hiroshima
Japan	Research Site	Kurume-shi	Fukuoka
Japan	Research Site	Kyoto-shi	Kyoto
Japan	Research Site	Matsuyama-shi	Ehime
Japan	Research Site	Miyazaki-shi	Miyazaki
Japan	Research Site	Nagoya-shi	Aichi
Japan	Research Site	Nagoya-shi	Aichi
Japan	Research Site	Niigata-shi	Niigata
Japan	Research Site	Osaka-shi	Osaka
Japan	Research Site	Osaka-shi	Osaka
Japan	Research Site	Shimotsuke-shi	Tochigi
Japan	Research Site	Suita-shi	Osaka
Japan	Research Site	Suntou-gun	Shizuoka
Japan	Research Site	Tokyo
Japan	Research Site	Tokyo
Japan	Research Site	Tokyo
Japan	Research Site	Tokyo
Japan	Research Site	Utsunomiya-shi	Tochigi
Korea, Republic of	Research Site	Goyang-si, Gyeonggi-do
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Latvia	Research Site	Daugavpils
Latvia	Research Site	Liepaja
Latvia	Research Site	Riga
Malaysia	Research Site	Kota Bharu	Kelantan
Malaysia	Research Site	Kuala Lumpur	Wilayah Persekutuan
Malaysia	Research Site	Kuala Lumpur	Wilayah Persekutuan
Malaysia	Research Site	Subang Jaya	Selangor (incl. Putrajaya)
Mexico	Research Site	Colima
Mexico	Research Site	Distrito Federal
Mexico	Research Site	Durango
Mexico	Research Site	Leon	Guanajuato
Mexico	Research Site	Mexico	Distrito Federal
Mexico	Research Site	Mexico City	Distrito Federal
Mexico	Research Site	Mexico City	Distrito Federal
Mexico	Research Site	Monterrey	Nuevo León
Mexico	Research Site	Pachuca de Soto	Hidalgo
Mexico	Research Site	Queretaro	Querétaro
Mexico	Research Site	San Luis Potosi	San Luis PotosÃ-
Mexico	Research Site	Toluca
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Bergen op Zoom
Netherlands	Research Site	Breda
Netherlands	Research Site	Capelle aan den ijssel
Netherlands	Research Site	Den Haag
Netherlands	Research Site	Dordrecht
Netherlands	Research Site	Hoofddorp
Netherlands	Research Site	Leiden
Netherlands	Research Site	Nieuwegein
Netherlands	Research Site	Rotterdam
Netherlands	Research Site	Rotterdam
Netherlands	Research Site	Schiedam
Netherlands	Research Site	Sittard-Geleen
Netherlands	Research Site	Tiel
Netherlands	Research Site	Tilburg
Netherlands	Research Site	Venlo
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Philippines	Research Site	Cebu City
Philippines	Research Site	Manila
Philippines	Research Site	Manila
Philippines	Research Site	Metro Manila
Philippines	Research Site	Quezon City
Poland	Research Site	Gdansk
Poland	Research Site	Gdansk
Poland	Research Site	Krakow
Poland	Research Site	Olsztyn
Poland	Research Site	Poznan
Poland	Research Site	Rzeszow
Poland	Research Site	Szczecin
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Porto
Portugal	Research Site	Porto
Portugal	Research Site	Santa Maria da Feira
Romania	Research Site	Bucharest
Romania	Research Site	Craiova
Romania	Research Site	Sibiu
Romania	Research Site	Suceava
Romania	Research Site	Timisoara
Russian Federation	Research Site	Barnaul
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Ivanovo
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Serbia	Research Site	Belgrade
Serbia	Research Site	Nis
Slovakia	Research Site	Bardejov
Slovakia	Research Site	Kosice
Slovakia	Research Site	Michalovce
Slovakia	Research Site	Poprad
Slovakia	Research Site	Presov
Slovakia	Research Site	Spisska Nova Ves
Slovakia	Research Site	Trebisov
Slovenia	Research Site	Ljublijana
Slovenia	Research Site	Maribor
South Africa	Research Site	Cape Town
South Africa	Research Site	Groenkloof	Gauteng
South Africa	Research Site	Johannesburg	Gauteng
South Africa	Research Site	Pietermaritzburg
South Africa	Research Site	Port Elizabeth
South Africa	Research Site	Pretoria
South Africa	Research Site	Pretoria
Spain	Research Site	A Coruña	Galicia
Spain	Research Site	A Coruña	Galicia
Spain	Research Site	Alcorcón	Madrid
Spain	Research Site	Badalona	Cataluña
Spain	Research Site	Barcelona	Cataluña
Spain	Research Site	Barcelona	Cataluña
Spain	Research Site	Barcelona	Cataluña
Spain	Research Site	Barcelona	Cataluña
Spain	Research Site	Cádiz	AndalucÃ-a
Spain	Research Site	Córdoba	AndalucÃ-a
Spain	Research Site	Elche	Comunidad Valenciana
Spain	Research Site	Girona	Cataluña
Spain	Research Site	Jaén	AndalucÃ-a
Spain	Research Site	Lleida	Cataluña
Spain	Research Site	Málaga	AndalucÃ-a
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Sabadell	Cataluña
Spain	Research Site	Santander	Cantabria
Spain	Research Site	Sevilla	AndalucÃ-a
Spain	Research Site	Valencia	Comunidad Valenciana
Spain	Research Site	Valencia	Comunidad Valenciana
Spain	Research Site	Zaragoza	Aragón
Taiwan	Research Site	Keelung City	Keelung
Taiwan	Research Site	Putzu City	Chiayi
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Turkey	Research Site	Ä°zmir
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Bornova-Izmir
United Kingdom	Research Site	Bebington
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Brighton
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Dorset
United Kingdom	Research Site	Guildford
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Newcastle
United Kingdom	Research Site	Peterborough
United Kingdom	Research Site	Plymouth
United Kingdom	Research Site	Poole
United Kingdom	Research Site	Portsmouth
United Kingdom	Research Site	Sheffield
United Kingdom	Research Site	Truro
United States	Research Site	Abilene	Texas
United States	Research Site	Alhambra	California
United States	Research Site	Anaheim	California
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Annapolis	Maryland
United States	Research Site	Asheville	North Carolina
United States	Research Site	Athens	Georgia
United States	Research Site	Baltimore	Maryland
United States	Research Site	Bethesda	Maryland
United States	Research Site	Beverly Hills	California
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boynton Beach	Florida
United States	Research Site	Campbell	California
United States	Research Site	Cedar Rapids	Iowa
United States	Research Site	Charleston	South Carolina
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Columbia	South Carolina
United States	Research Site	Columbia	Maryland
United States	Research Site	Columbus	Ohio
United States	Research Site	Coral Springs	Florida
United States	Research Site	Corpus Christi	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Danvers	Massachusetts
United States	Research Site	Denver	Colorado
United States	Research Site	Denville	New Jersey
United States	Research Site	Detroit	Michigan
United States	Research Site	East Setauket	New York
United States	Research Site	Edina	Minnesota
United States	Research Site	El Paso	Texas
United States	Research Site	Fort Lauderdale	Florida
United States	Research Site	Fresno	California
United States	Research Site	Fullerton	California
United States	Research Site	Garland	Texas
United States	Research Site	Germantown	Tennessee
United States	Research Site	Grand Junction	Colorado
United States	Research Site	Hackensack	New Jersey
United States	Research Site	Henderson	Nevada
United States	Research Site	Hershey	Pennsylvania
United States	Research Site	High Point	North Carolina
United States	Research Site	Hilton Head Island	South Carolina
United States	Research Site	Hollywood	Florida
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Hutchinson	Kansas
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Jackson	Mississippi
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jefferson City	Missouri
United States	Research Site	Jonesboro	Arkansas
United States	Research Site	La Verne	California
United States	Research Site	Lancaster	California
United States	Research Site	Lebanon	New Hampshire
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Long Beach	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Melbourne	Florida
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Niles	Illinois
United States	Research Site	Northridge	California
United States	Research Site	Nyack	New York
United States	Research Site	Paducah	Kentucky
United States	Research Site	Pawtucket	Rhode Island
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Plano	Texas
United States	Research Site	Redondo Beach	California
United States	Research Site	Richlands	Virginia
United States	Research Site	Richmond	Virginia
United States	Research Site	Roanoke	Virginia
United States	Research Site	Saint Louis Park	Minnesota
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	Santa Barbara	California
United States	Research Site	Santa Maria	California
United States	Research Site	Seattle	Washington
United States	Research Site	Seattle	Washington
United States	Research Site	Sioux Falls	South Dakota
United States	Research Site	Tacoma	Washington
United States	Research Site	Torrance	California
United States	Research Site	Tucson	Arizona
United States	Research Site	Tulsa	Oklahoma
United States	Research Site	Tyler	Texas
United States	Research Site	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Amgen	Daiichi Sankyo, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  Czechia,  Denmark,  France,  Germany,  Greece,  Hong Kong,  Hungary,  India,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Latvia,  Malaysia,  Mexico,  Netherlands,  Peru,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Slovakia,  Slovenia,  South Africa,  Spain,  Taiwan,  Turkey,  United Kingdom, 

References & Publications (2)

Coleman R, Finkelstein DM, Barrios C, Martin M, Iwata H, Hegg R, Glaspy J, Periañez AM, Tonkin K, Deleu I, Sohn J, Crown J, Delaloge S, Dai T, Zhou Y, Jandial D, Chan A. Adjuvant denosumab in early breast cancer (D-CARE): an international, multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2020 Jan;21(1):60-72. doi: 10.1016/S1470-2045(19)30687-4. Epub 2019 Dec 2. — View Citation

Coleman R, Zhou Y, Jandial D, Cadieux B, Chan A. Bone Health Outcomes from the International, Multicenter, Randomized, Phase 3, Placebo-Controlled D-CARE Study Assessing Adjuvant Denosumab in Early Breast Cancer. Adv Ther. 2021 Aug;38(8):4569-4580. doi: 10.1007/s12325-021-01812-9. Epub 2021 Jun 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bone Metastasis-free Survival (BMFS)	BMFS time was defined as the time interval from the randomization date to the first occurrence of bone metastasis or death from any cause, whichever came first. Participants last known to be alive with no bone metastasis were censored at their last assessment date, or at the primary analysis data cut-off date, whichever was first. Participants who had first occurrence of bone metastasis before randomization were censored at their randomization date.; Bone metastasis must have been confirmed by central imaging analysis or by biopsy, Evidence of disseminated tumor cells in bone marrow was not sufficient for determination of disease recurrence. Development of new primary malignancy in bone was not considered as bone metastasis.; Since the median BMSF time could not be estimated due to low number of events, the percentage of participants with an event (i.e., bone metastasis or death) is reported.	From randomization until the primary analysis data cut-off date of 31 August 2017; median (minimum, maximum) time on study was 67.2 (0.0, 85.9) and 67.0 (0.0, 86.6) months in each treatment group respectively.
Secondary	Disease-free Survival (DFS)	DFS time was defined as the time interval from the randomization date to the date of first observation of disease recurrence or death from any cause, whichever was first. Participants last known to be alive with no disease recurrence were censored at their last assessment date, or at the primary analysis data cut-off date, whichever was first. Participants who had first disease recurrence before randomization were censored at their randomization date.; Disease recurrence includes bone metastasis and extraosseous disease (EOD) confirmed by central imaging analysis or by biopsy/cytology. Development of non-breast cancer new primary malignancy was not considered as disease recurrence.; Since the median DFS time could not be estimated due to low number of events, the percentage of participants with an event (i.e., disease recurrence or death) is reported.	From randomization until the primary analysis data cut-off date of 31 August 2017; median (minimum, maximum) time on study was 67.2 (0.0, 85.9) and 67.0 (0.0, 86.6) months in each treatment group respectively.
Secondary	Disease-free Survival (DFS) in the Postmenopausal Subset	DFS time was defined as the time interval from the randomization date to the date of first observation of disease recurrence or death from any cause, whichever was first. Participants last known to be alive with no disease recurrence were censored at their last assessment date, or at the primary analysis data cut-off date, whichever was first. Participants who had first disease recurrence before randomization were censored at their randomization date.; Disease recurrence includes bone metastasis and extraosseous disease (EOD) confirmed by central imaging analysis or by biopsy/cytology. Development of non-breast cancer new primary malignancy was not considered as disease recurrence.; Since the median DFS time in the postmenopausal subset could not be estimated due to low number of events, the percentage of participants with an event (i.e., disease recurrence or death) is reported.	From randomization until the primary analysis data cut-off date of 31 August 2017; median (minimum, maximum) time on study was 67.2 (0.0, 85.9) and 67.0 (0.0, 86.6) months in each treatment group respectively.
Secondary	Overall Survival	Overall survival (OS) time was defined as the time interval from the randomization date to the date of death from any cause. Participants last known to be alive were censored at their last contact date.; Since the median time to overall survival could not be estimated at the time of the final analysis due to low numbers of events, the percentage of participants with an event (i.e., death) is reported.	From randomization until the end of study; median (minimum, maximum) time on study was 72.7 (0, 92) and 72.3 (0, 92) months in each treatment group respectively.
Secondary	Distant Recurrence-free Survival	Distant recurrence-free survival (DRFS) was defined as the time interval from the randomization date to the date of first observation of distant disease recurrence or death from any cause, whichever came first. Participants last known to be alive, who had not experienced distant disease recurrence, were censored at their last assessment date, or at the primary analysis data cut-off date, whichever was first. Participants who had first distant recurrence before randomization were censored at their randomization date.; Distant disease recurrence includes confirmed bone metastasis and extraosseous disease other than local-regional disease recurrence. Development of non-breast cancer new primary malignancy was not considered as distant disease recurrence.; Since the median time to DRFS could not be estimated due to the low number of events, the percentage of participants with an event (i.e., distant recurrence or death) is reported.	From randomization until the primary analysis data cut-off date of 31 August 2017; median (minimum, maximum) time on study was 67.2 (0.0, 85.9) and 67.0 (0.0, 86.6) months in each treatment group respectively.

External Links

•   AmgenTrials clinical trials website