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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Placebo; Drug: Denosumab

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 4509
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Quilmes, Buenos Aires, Argentina, B1878GEG
      • Research Site
    • Quilmes, Buenos Aires, Argentina, B1878DVB
      • Research Site
    • San Martin, Buenos Aires, Argentina, B1650BOB
      • Research Site
  • Neuquén
    • Neuquen, Neuquén, Argentina, Q8300HDH
      • Research Site
  • Santa Fe
    • Provincia De Santa Fe, Santa Fe, Argentina, S3000FFV
      • Research Site
  • Tucuman
    • San Miguel de Tucuman, Tucuman, Argentina, T4000GTB
      • Research Site
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Research Site
    • Caringbah, New South Wales, Australia, 2229
      • Research Site
    • Kogarah, New South Wales, Australia, 2217
      • Research Site
    • Tweed Heads, New South Wales, Australia, 2485
      • Research Site
    • Wahroonga, New South Wales, Australia, 2076
      • Research Site
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Research Site
  • Victoria
    • Bentleigh East, Victoria, Australia, 3165
      • Research Site
    • East Melbourne, Victoria, Australia, 3002
      • Research Site
    • Fitzroy, Victoria, Australia, 3065
      • Research Site
    • Footscray, Victoria, Australia, 3011
      • Research Site
    • Frankston, Victoria, Australia, 3199
      • Research Site
    • Heidelberg, Victoria, Australia, 3084
      • Research Site
    • Malvern, Victoria, Australia, 3144
      • Research Site
    • Parkville, Victoria, Australia, 3050
      • Research Site
    • Richmond, Victoria, Australia, 3121
      • Research Site
    • Ringwood East, Victoria, Australia, 3135
      • Research Site
    • Warrnambool, Victoria, Australia, 3280
      • Research Site
    • Wodonga, Victoria, Australia, 3690
      • Research Site
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Research Site
    • Subiaco, Western Australia, Australia, 6008
      • Research Site
• Belgium
  • Antwerpen, Belgium, 2020
    • Research Site
  • Bonheiden, Belgium, 2820
    • Research Site
  • Brugge, Belgium, 8000
    • Research Site
  • Brussel, Belgium, 1090
    • Research Site
  • Bruxelles, Belgium, 1200
    • Research Site
  • Bruxelles, Belgium, 1020
    • Research Site
  • Edegem, Belgium, 2650
    • Research Site
  • Gent, Belgium, 9000
    • Research Site
  • Hasselt, Belgium, 3500
    • Research Site
  • Kortrijk, Belgium, 8500
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Libramont, Belgium, 6800
    • Research Site
  • Liège, Belgium, 4000
    • Research Site
  • Namur, Belgium, 5000
    • Research Site
  • Oostende, Belgium, 8400
    • Research Site
  • Ottignies, Belgium, 1340
    • Research Site
  • Sint-Niklaas, Belgium, 9100
    • Research Site
  • Tournai, Belgium, 7500
    • Research Site
  • Wilrijk, Belgium, 2610
    • Research Site
  • Yvoir, Belgium, 5530
    • Research Site
• Brazil
  • São Paulo, Brazil, 01317-000
    • Research Site
  • São Paulo, Brazil, 01246-000
    • Research Site
  • Bahia
    • Salvador, Bahia, Brazil, 40950-640
      • Research Site
    • Salvador, Bahia, Brazil, 41820-021
      • Research Site
  • Paraná
    • Curitiba, Paraná, Brazil, 81520-060
      • Research Site
    • Londrina, Paraná, Brazil, 86050-190
      • Research Site
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-003
      • Research Site
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
      • Research Site
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90050-170
      • Research Site
  • Santa Catarina
    • ItajaÃ-, Santa Catarina, Brazil, 88301-220
      • Research Site
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784-400
      • Research Site
    • Santo Andre, São Paulo, Brazil, 09080-110
      • Research Site
    • Sao Paulo, São Paulo, Brazil, 04038-034
      • Research Site
• Bulgaria
  • Plovdiv, Bulgaria, 4004
    • Research Site
  • Rousse, Bulgaria, 7002
    • Research Site
  • Sofia, Bulgaria, 1784
    • Research Site
  • Sofia, Bulgaria, 1756
    • Research Site
  • Stara Zagora, Bulgaria, 6003
    • Research Site
  • Varna, Bulgaria, 9000
    • Research Site
  • Veliko Tarnovo, Bulgaria, 5000
    • Research Site
• Canada
  • Quebec, Canada, G1S 4L8
    • Research Site
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Research Site
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Research Site
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • Research Site
    • Victoria, British Columbia, Canada, V8R 6V5
      • Research Site
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Research Site
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Research Site
  • Nova Scotia
    • Sydney, Nova Scotia, Canada, B1P 1P3
      • Research Site
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Research Site
    • Brampton, Ontario, Canada, L6R 3J7
      • Research Site
    • Kingston, Ontario, Canada, K7L 5P9
      • Research Site
    • Kitchener, Ontario, Canada, N2G 1G3
      • Research Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Research Site
    • Sault Ste. Marie, Ontario, Canada, P6B 0A8
      • Research Site
    • Sudbury, Ontario, Canada, P3E 5J1
      • Research Site
    • Toronto, Ontario, Canada, M9N 1N8
      • Research Site
    • Toronto, Ontario, Canada, M4C 3E7
      • Research Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Research Site
    • Montreal, Quebec, Canada, H3T 1E2
      • Research Site
    • Montreal, Quebec, Canada, H1T 2M4
      • Research Site
    • Montreal, Quebec, Canada, H2W 1T8
      • Research Site
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Research Site
• Chile
  • Santiago, Chile, 8380455
    • Research Site
  • CautÃ-n
    • Temuco, CautÃ-n, Chile, 4810469
      • Research Site
  • ValparaÃ-so
    • Vina del Mar, ValparaÃ-so, Chile, 2520612
      • Research Site
• Czechia
  • Brno, Czechia, 656 53
    • Research Site
  • Brno, Czechia, 625 00
    • Research Site
  • Chomutov, Czechia, 430 12
    • Research Site
  • Horovice, Czechia, 268 31
    • Research Site
  • Hradec Kralove, Czechia, 500 05
    • Research Site
  • Olomouc, Czechia, 775 20
    • Research Site
  • Praha 10, Czechia, 100 34
    • Research Site
  • Praha 10, Czechia, 100 00
    • Research Site
  • Praha 4, Czechia, 140 44
    • Research Site
  • Praha 5, Czechia, 150 06
    • Research Site
  • Praha 8, Czechia, 180 81
    • Research Site
• Denmark
  • Herning, Denmark, 7400
    • Research Site
  • Vejle, Denmark, 7100
    • Research Site
  • Viborg, Denmark, 8800
    • Research Site
  • Ã…rhus C, Denmark, 8000
    • Research Site
• France
  • Angers, France, 49933
    • Research Site
  • Bordeaux Cedex, France, 33030
    • Research Site
  • Dijon, France, 21079
    • Research Site
  • Grenoble, France, 38000
    • Research Site
  • Hyères, France, 83400
    • Research Site
  • Le Mans, France, 72000
    • Research Site
  • Lille, France, 59000
    • Research Site
  • Monaco, France, 98012
    • Research Site
  • Nantes Cedex 2, France, 44202
    • Research Site
  • Paris, France, 75012
    • Research Site
  • Pierre-Benite, France, 69495
    • Research Site
  • Saint Priest en Jarez Cedex, France, 42270
    • Research Site
  • Strasbourg cedex, France, 67091
    • Research Site
  • Villejuif cedex, France, 94805
    • Research Site
• Germany
  • Berlin, Germany, 10117
    • Research Site
  • Berlin, Germany, 10713
    • Research Site
  • Bonn, Germany, 53111
    • Research Site
  • Bottrop, Germany, 46236
    • Research Site
  • Erlangen, Germany, 91054
    • Research Site
  • Frankfurt, Germany, 60590
    • Research Site
  • Kiel, Germany, 24105
    • Research Site
  • Koblenz, Germany, 56068
    • Research Site
  • Mannheim, Germany, 68161
    • Research Site
  • München, Germany, 80335
    • Research Site
  • München, Germany, 80638
    • Research Site
  • München, Germany, 81675
    • Research Site
  • Recklinghausen, Germany, 45657
    • Research Site
  • Rostock, Germany, 18059
    • Research Site
  • Trier, Germany, 54290
    • Research Site
  • Tübingen, Germany, 72076
    • Research Site
• Greece
  • Athens, Greece, 11528
    • Research Site
  • Athens, Greece, 11522
    • Research Site
  • Heraklion, Greece, 71110
    • Research Site
  • Patra, Greece, 26500
    • Research Site
  • Thessaloniki, Greece, 54636
    • Research Site
  • Thessaloniki, Greece, 56429
    • Research Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Research Site
  • New Territories, Hong Kong
    • Research Site
• Hungary
  • Budapest, Hungary, 1125
    • Research Site
  • Budapest, Hungary, 1145
    • Research Site
  • Budapest, Hungary, 1122
    • Research Site
  • Budapest, Hungary, 1062
    • Research Site
  • Budapest, Hungary, 1082
    • Research Site
  • Budapest, Hungary, 1032
    • Research Site
  • Debrecen, Hungary, 4012
    • Research Site
  • Gyor, Hungary, 9023
    • Research Site
  • Nyiregyhaza, Hungary, 4400
    • Research Site
  • Pecs, Hungary, 7624
    • Research Site
  • Szeged, Hungary, 6725
    • Research Site
  • Szekesfehervar, Hungary, 8000
    • Research Site
  • Szolnok, Hungary, 5004
    • Research Site
  • Zalaegerszeg, Hungary, 8900
    • Research Site
• India
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500 024
      • Research Site
  • Karnataka
    • Bangalore, Karnataka, India, 560 054
      • Research Site
  • Maharashtra
    • Ahmednagar, Maharashtra, India, 413 736
      • Research Site
    • Aurangabad, Maharashtra, India, 431 001
      • Research Site
    • Miraj, Maharashtra, India, 416 410
      • Research Site
    • Mumbai, Maharashtra, India, 400 012
      • Research Site
    • Mumbai, Maharashtra, India, 400 016
      • Research Site
    • Nashik, Maharashtra, India, 422 005
      • Research Site
    • Nashik, Maharashtra, India, 422 004
      • Research Site
    • Pune, Maharashtra, India, 411 001
      • Research Site
  • Rajasthan
    • Jaipur, Rajasthan, India, 302 013
      • Research Site
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600 018
      • Research Site
    • Madurai, Tamil Nadu, India, 625 107
      • Research Site
• Ireland
  • Cork, Ireland
    • Research Site
  • Dublin, Ireland, 4
    • Research Site
  • Dublin, Ireland, 8
    • Research Site
  • Dublin, Ireland, 9
    • Research Site
  • Limerick, Ireland
    • Research Site
  • Waterford, Ireland
    • Research Site
• Israel
  • Ashkelon, Israel, 78278
    • Research Site
  • Haifa, Israel, 31096
    • Research Site
  • Jerusalem, Israel, 91031
    • Research Site
  • Kfar Sava, Israel, 44281
    • Research Site
  • Petah Tikva, Israel, 49100
    • Research Site
  • Poria Eylit, Israel, 15208
    • Research Site
  • Rehovot, Israel, 76100
    • Research Site
  • Tel Aviv, Israel, 64239
    • Research Site
  • Tel Aviv, Israel, 69710
    • Research Site
• Italy
  • Ancona, Italy, 60131
    • Research Site
  • Bari, Italy, 70124
    • Research Site
  • Brescia, Italy, 25123
    • Research Site
  • Meldola FC, Italy, 47014
    • Research Site
  • Milano, Italy, 20142
    • Research Site
  • Monza (MB), Italy, 20900
    • Research Site
  • Palermo, Italy, 90100
    • Research Site
  • Parma, Italy, 43100
    • Research Site
  • San Giovanni Rotondo FG, Italy, 71013
    • Research Site
  • Treviglio (BG), Italy, 24047
    • Research Site
  • Varese, Italy, 21100
    • Research Site
• Japan
  • Tokyo, Japan, 135-8550
    • Research Site
  • Tokyo, Japan, 142-8666
    • Research Site
  • Tokyo, Japan, 160-0023
    • Research Site
  • Tokyo, Japan, 173-0003
    • Research Site
  • Aichi
    • Nagoya-shi, Aichi, Japan, 464-8681
      • Research Site
    • Nagoya-shi, Aichi, Japan, 467-8602
      • Research Site
  • Ehime
    • Matsuyama-shi, Ehime, Japan, 791-0280
      • Research Site
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 811-1395
      • Research Site
    • Kitakyushu-shi, Fukuoka, Japan, 802-0077
      • Research Site
    • Kurume-shi, Fukuoka, Japan, 830-0013
      • Research Site
  • Hiroshima
    • Kure-shi, Hiroshima, Japan, 737-0023
      • Research Site
  • Hyogo
    • Akashi-shi, Hyogo, Japan, 673-8558
      • Research Site
  • Kagoshima
    • Kagoshima-shi, Kagoshima, Japan, 892-0833
      • Research Site
  • Kanagawa
    • Isehara-shi, Kanagawa, Japan, 259-1193
      • Research Site
  • Kumamoto
    • Kumamoto-shi, Kumamoto, Japan, 860-8556
      • Research Site
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 606-8507
      • Research Site
  • Miyazaki
    • Miyazaki-shi, Miyazaki, Japan, 880-0052
      • Research Site
  • Niigata
    • Niigata-shi, Niigata, Japan, 951-8566
      • Research Site
  • Okayama
    • Kurashiki-shi, Okayama, Japan, 701-0192
      • Research Site
  • Osaka
    • Osaka-shi, Osaka, Japan, 540-0006
      • Research Site
    • Osaka-shi, Osaka, Japan, 537-8511
      • Research Site
    • Suita-shi, Osaka, Japan, 565-0871
      • Research Site
  • Saitama
    • Hidaka-Shi, Saitama, Japan, 350-1298
      • Research Site
    • Kitaadachi-gun, Saitama, Japan, 362-0806
      • Research Site
  • Shizuoka
    • Suntou-gun, Shizuoka, Japan, 411-8777
      • Research Site
  • Tochigi
    • Shimotsuke-shi, Tochigi, Japan, 329-0498
      • Research Site
    • Utsunomiya-shi, Tochigi, Japan, 320-0834
      • Research Site
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Research Site
• Korea, Republic of
  • Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769
    • Research Site
  • Incheon, Korea, Republic of, 405-835
    • Research Site
  • Seoul, Korea, Republic of, 135-710
    • Research Site
  • Seoul, Korea, Republic of, 120-752
    • Research Site
  • Seoul, Korea, Republic of, 110-744
    • Research Site
• Latvia
  • Daugavpils, Latvia, 5417
    • Research Site
  • Liepaja, Latvia, 3401
    • Research Site
  • Riga, Latvia, 1079
    • Research Site
• Malaysia
  • Kelantan
    • Kota Bharu, Kelantan, Malaysia, 16150
      • Research Site
  • Selangor (incl. Putrajaya)
    • Subang Jaya, Selangor (incl. Putrajaya), Malaysia, 47500
      • Research Site
  • Wilayah Persekutuan
    • Kuala Lumpur, Wilayah Persekutuan, Malaysia, 56000
      • Research Site
    • Kuala Lumpur, Wilayah Persekutuan, Malaysia, 50703
      • Research Site
• Mexico
  • Colima, Mexico, 28030
    • Research Site
  • Distrito Federal, Mexico, 11000
    • Research Site
  • Durango, Mexico, 34000
    • Research Site
  • Toluca, Mexico, 50180
    • Research Site
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 01120
      • Research Site
    • Mexico City, Distrito Federal, Mexico, 06726
      • Research Site
    • Mexico City, Distrito Federal, Mexico, 07760
      • Research Site
  • Guanajuato
    • Leon, Guanajuato, Mexico, 37670
      • Research Site
  • Hidalgo
    • Pachuca de Soto, Hidalgo, Mexico, 42084
      • Research Site
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64000
      • Research Site
  • Querétaro
    • Queretaro, Querétaro, Mexico, 76178
      • Research Site
  • San Luis PotosÃ-
    • San Luis Potosi, San Luis PotosÃ-, Mexico, 78200
      • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Research Site
  • Bergen op Zoom, Netherlands, 4624 VT
    • Research Site
  • Breda, Netherlands, 4819 EV
    • Research Site
  • Capelle aan den ijssel, Netherlands, 2906 ZC
    • Research Site
  • Den Haag, Netherlands, 2545 CH
    • Research Site
  • Dordrecht, Netherlands, 3318 AT
    • Research Site
  • Hoofddorp, Netherlands, 2134 TM
    • Research Site
  • Leiden, Netherlands, 2333 ZA
    • Research Site
  • Nieuwegein, Netherlands, 3435 CM
    • Research Site
  • Rotterdam, Netherlands, 3075 EA
    • Research Site
  • Rotterdam, Netherlands, 3045 PM
    • Research Site
  • Schiedam, Netherlands, 3118 JH
    • Research Site
  • Sittard-Geleen, Netherlands, 6162 BG
    • Research Site
  • Tiel, Netherlands, 4002 WP
    • Research Site
  • Tilburg, Netherlands, 5022 GC
    • Research Site
  • Venlo, Netherlands, 5912 BL
    • Research Site
• Peru
  • Lima, Peru, LIMA 27
    • Research Site
  • Lima, Peru, Lima 18
    • Research Site
  • Lima, Peru, LIMA 11
    • Research Site
• Philippines
  • Cebu City, Philippines, 6000
    • Research Site
  • Manila, Philippines, 1000
    • Research Site
  • Manila, Philippines, 1008
    • Research Site
  • Metro Manila, Philippines, 1100
    • Research Site
  • Quezon City, Philippines, 1102
    • Research Site
• Poland
  • Gdansk, Poland, 80-952
    • Research Site
  • Gdansk, Poland, 80-219
    • Research Site
  • Krakow, Poland, 31-108
    • Research Site
  • Olsztyn, Poland, 10-228
    • Research Site
  • Poznan, Poland, 61-485
    • Research Site
  • Rzeszow, Poland, 35-021
    • Research Site
  • Szczecin, Poland, 71-730
    • Research Site
• Portugal
  • Lisboa, Portugal, 1099-023
    • Research Site
  • Lisboa, Portugal, 1500-650
    • Research Site
  • Porto, Portugal, 4200-319
    • Research Site
  • Porto, Portugal, 4200-072
    • Research Site
  • Santa Maria da Feira, Portugal, 4520-211
    • Research Site
• Romania
  • Bucharest, Romania, 022328
    • Research Site
  • Craiova, Romania, 200385
    • Research Site
  • Sibiu, Romania, 550245
    • Research Site
  • Suceava, Romania, 720237
    • Research Site
  • Timisoara, Romania, 300239
    • Research Site
• Russian Federation
  • Barnaul, Russian Federation, 656049
    • Research Site
  • Chelyabinsk, Russian Federation, 454076
    • Research Site
  • Ivanovo, Russian Federation, 153013
    • Research Site
  • Kazan, Russian Federation, 420029
    • Research Site
  • Moscow, Russian Federation, 115478
    • Research Site
  • Saint Petersburg, Russian Federation, 195271
    • Research Site
  • Saint Petersburg, Russian Federation, 197022
    • Research Site
• Serbia
  • Belgrade, Serbia, 11000
    • Research Site
  • Nis, Serbia, 18000
    • Research Site
• Slovakia
  • Bardejov, Slovakia, 085 01
    • Research Site
  • Kosice, Slovakia, 041 91
    • Research Site
  • Michalovce, Slovakia, 071 01
    • Research Site
  • Poprad, Slovakia, 058 01
    • Research Site
  • Presov, Slovakia, 080 01
    • Research Site
  • Spisska Nova Ves, Slovakia, 052 01
    • Research Site
  • Trebisov, Slovakia, 075 01
    • Research Site
• Slovenia
  • Ljublijana, Slovenia, 1525
    • Research Site
  • Maribor, Slovenia, 2000
    • Research Site
• South Africa
  • Cape Town, South Africa, 7925
    • Research Site
  • Pietermaritzburg, South Africa, 3201
    • Research Site
  • Port Elizabeth, South Africa, 6045
    • Research Site
  • Pretoria, South Africa, 0002
    • Research Site
  • Pretoria, South Africa, 0081
    • Research Site
  • Gauteng
    • Groenkloof, Gauteng, South Africa, 0181
      • Research Site
    • Johannesburg, Gauteng, South Africa, 2196
      • Research Site
• Spain
  • Madrid, Spain, 28040
    • Research Site
  • Madrid, Spain, 28009
    • Research Site
  • Madrid, Spain, 28050
    • Research Site
  • AndalucÃ-a
    • Cádiz, AndalucÃ-a, Spain, 11009
      • Research Site
    • Córdoba, AndalucÃ-a, Spain, 14004
      • Research Site
    • Jaén, AndalucÃ-a, Spain, 23007
      • Research Site
    • Málaga, AndalucÃ-a, Spain, 29010
      • Research Site
    • Sevilla, AndalucÃ-a, Spain, 41013
      • Research Site
  • Aragón
    • Zaragoza, Aragón, Spain, 50009
      • Research Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Research Site
  • Cataluña
    • Badalona, Cataluña, Spain, 08916
      • Research Site
    • Barcelona, Cataluña, Spain, 08003
      • Research Site
    • Barcelona, Cataluña, Spain, 08035
      • Research Site
    • Barcelona, Cataluña, Spain, 08036
      • Research Site
    • Barcelona, Cataluña, Spain, 08041
      • Research Site
    • Girona, Cataluña, Spain, 17007
      • Research Site
    • Lleida, Cataluña, Spain, 25198
      • Research Site
    • Sabadell, Cataluña, Spain, 08208
      • Research Site
  • Comunidad Valenciana
    • Elche, Comunidad Valenciana, Spain, 03203
      • Research Site
    • Valencia, Comunidad Valenciana, Spain, 46009
      • Research Site
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Research Site
  • Galicia
    • A Coruña, Galicia, Spain, 15006
      • Research Site
    • A Coruña, Galicia, Spain, 15009
      • Research Site
  • Madrid
    • Alcorcón, Madrid, Spain, 28922
      • Research Site
• Taiwan
  • Tainan, Taiwan, 704
    • Research Site
  • Taipei, Taiwan, 10002
    • Research Site
  • Chiayi
    • Putzu City, Chiayi, Taiwan, 61363
      • Research Site
  • Keelung
    • Keelung City, Keelung, Taiwan, 20401
      • Research Site
• Turkey
  • Ankara, Turkey, 06100
    • Research Site
  • Ankara, Turkey, 06500
    • Research Site
  • Bornova-Izmir, Turkey, 35100
    • Research Site
  • Ä°zmir, Turkey, 35340
    • Research Site
• United Kingdom
  • Bebington, United Kingdom, CH63 4JY
    • Research Site
  • Birmingham, United Kingdom, B15 2TT
    • Research Site
  • Brighton, United Kingdom, BN2 5BE
    • Research Site
  • Bristol, United Kingdom, BS2 8ED
    • Research Site
  • Cambridge, United Kingdom, CB2 0QQ
    • Research Site
  • Dorset, United Kingdom, BH7 7DW
    • Research Site
  • Guildford, United Kingdom, GU2 7XX
    • Research Site
  • Leeds, United Kingdom, LS9 7TF
    • Research Site
  • London, United Kingdom, SW3 6JJ
    • Research Site
  • London, United Kingdom, W2 1NY
    • Research Site
  • Manchester, United Kingdom, M20 4BX
    • Research Site
  • Manchester, United Kingdom, M23 9LT
    • Research Site
  • Newcastle, United Kingdom, NE4 6BE
    • Research Site
  • Peterborough, United Kingdom, PE3 9GZ
    • Research Site
  • Plymouth, United Kingdom, PL6 8DH
    • Research Site
  • Poole, United Kingdom, BH15 2JB
    • Research Site
  • Portsmouth, United Kingdom, PO6 3LY
    • Research Site
  • Sheffield, United Kingdom, S10 2SJ
    • Research Site
  • Truro, United Kingdom, TR1 3LJ
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Research Site
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Research Site
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Research Site
  • California
    • Alhambra, California, United States, 91801
      • Research Site
    • Anaheim, California, United States, 92801
      • Research Site
    • Beverly Hills, California, United States, 90211
      • Research Site
    • Campbell, California, United States, 95008
      • Research Site
    • Fresno, California, United States, 93720
      • Research Site
    • Fullerton, California, United States, 92835
      • Research Site
    • La Verne, California, United States, 91750
      • Research Site
    • Lancaster, California, United States, 93534
      • Research Site
    • Long Beach, California, United States, 90813
      • Research Site
    • Los Angeles, California, United States, 90025
      • Research Site
    • Los Angeles, California, United States, 90024
      • Research Site
    • Los Angeles, California, United States, 90095-1772
      • Research Site
    • Northridge, California, United States, 91328
      • Research Site
    • Redondo Beach, California, United States, 90277
      • Research Site
    • Santa Barbara, California, United States, 93105
      • Research Site
    • Santa Maria, California, United States, 93454
      • Research Site
    • Torrance, California, United States, 90502
      • Research Site
  • Colorado
    • Denver, Colorado, United States, 80220
      • Research Site
    • Grand Junction, Colorado, United States, 81501
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Research Site
  • Florida
    • Boynton Beach, Florida, United States, 33435
      • Research Site
    • Coral Springs, Florida, United States, 33065
      • Research Site
    • Fort Lauderdale, Florida, United States, 33316
      • Research Site
    • Hollywood, Florida, United States, 33021
      • Research Site
    • Jacksonville, Florida, United States, 32256
      • Research Site
    • Melbourne, Florida, United States, 32901
      • Research Site
  • Georgia
    • Athens, Georgia, United States, 30607
      • Research Site
  • Illinois
    • Niles, Illinois, United States, 60714
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Research Site
  • Iowa
    • Cedar Rapids, Iowa, United States, 52402
      • Research Site
  • Kansas
    • Hutchinson, Kansas, United States, 67502
      • Research Site
    • Wichita, Kansas, United States, 67214
      • Research Site
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Research Site
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Research Site
    • Baltimore, Maryland, United States, 21201
      • Research Site
    • Bethesda, Maryland, United States, 20817
      • Research Site
    • Columbia, Maryland, United States, 21044
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Research Site
    • Danvers, Massachusetts, United States, 01923
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Research Site
    • Detroit, Michigan, United States, 48201
      • Research Site
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Research Site
    • Minneapolis, Minnesota, United States, 55407
      • Research Site
    • Saint Louis Park, Minnesota, United States, 55426
      • Research Site
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Research Site
  • Missouri
    • Jefferson City, Missouri, United States, 65109
      • Research Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Research Site
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Research Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0001
      • Research Site
  • New Jersey
    • Denville, New Jersey, United States, 07834
      • Research Site
    • Hackensack, New Jersey, United States, 07601
      • Research Site
  • New York
    • East Setauket, New York, United States, 11733
      • Research Site
    • New York, New York, United States, 10003
      • Research Site
    • New York, New York, United States, 10032
      • Research Site
    • New York, New York, United States, 10029
      • Research Site
    • Nyack, New York, United States, 10960
      • Research Site
  • North Carolina
    • Asheville, North Carolina, United States, 28806
      • Research Site
    • High Point, North Carolina, United States, 27262
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Research Site
    • Columbus, Ohio, United States, 43210
      • Research Site
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Research Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Research Site
    • Pittsburgh, Pennsylvania, United States, 15213
      • Research Site
  • Rhode Island
    • Pawtucket, Rhode Island, United States, 02860
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Research Site
    • Columbia, South Carolina, United States, 29210
      • Research Site
    • Hilton Head Island, South Carolina, United States, 29926
      • Research Site
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Research Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Research Site
    • Germantown, Tennessee, United States, 38138
      • Research Site
    • Nashville, Tennessee, United States, 37203
      • Research Site
  • Texas
    • Abilene, Texas, United States, 79606-5208
      • Research Site
    • Corpus Christi, Texas, United States, 78463
      • Research Site
    • Dallas, Texas, United States, 75246
      • Research Site
    • Dallas, Texas, United States, 75390
      • Research Site
    • Dallas, Texas, United States, 75230-2510
      • Research Site
    • El Paso, Texas, United States, 79902
      • Research Site
    • Garland, Texas, United States, 75042
      • Research Site
    • Houston, Texas, United States, 77030
      • Research Site
    • Houston, Texas, United States, 77024
      • Research Site
    • Plano, Texas, United States, 75075
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site
    • San Antonio, Texas, United States, 78217
      • Research Site
    • Tyler, Texas, United States, 75702
      • Research Site
  • Virginia
    • Richlands, Virginia, United States, 24641
      • Research Site
    • Richmond, Virginia, United States, 23230
      • Research Site
    • Roanoke, Virginia, United States, 24014
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98133
      • Research Site
    • Seattle, Washington, United States, 98109-1023
      • Research Site
    • Tacoma, Washington, United States, 98405
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Participants received placebo subcutaneous injections once every 4 weeks for 6 months followed by placebo subcutaneous injections once every 3 months for 4.5 years.	Drug: Placebo; Administered subcutaneously for up to 5 years
EXPERIMENTAL: Denosumab; Participants received denosumab 120 mg subcutaneous injections once every 4 weeks for 6 months followed by denosumab 120 mg subcutaneous injections once every 3 months for 4.5 years.	Drug: Denosumab; Administered subcutaneously for up to 5 years; Other Names: XGEVA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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.

Collaborators and Investigators

• Sponsor: Amgen
• Collaborators: Daiichi Sankyo, Inc.

Publications and helpful links

General Publications

• Coleman R, Finkelstein DM, Barrios C, Martin M, Iwata H, Hegg R, Glaspy J, Perianez 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.
• 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.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 2, 2010
• Primary Completion (ACTUAL): August 31, 2017
• Study Completion (ACTUAL): March 26, 2018

Study Registration Dates

• First Submitted: February 4, 2010
• First Submitted That Met QC Criteria: February 25, 2010
• First Posted (ESTIMATE): February 26, 2010

Study Record Updates

• Last Update Posted (ACTUAL): September 28, 2021
• Last Update Submitted That Met QC Criteria: September 1, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Early Stage Breast Cancer; Stage II breast cancer; Stage III breast cancer; Breast Neoplasms; Breast Tumors; Bone Metastasis; Adjuvant treatment; Neoadjuvant treatment; Denosumab; Early breast cancer; Stage IIIA breast cancer; Stage IIIB breast cancer; Stage IIA breast cancer; Stage IIB breast cancer; Stage IIIC breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: 20060359; 2009-011299-32 (EUDRACT_NUMBER)