Breast CancerPhase 3NCT01077154
Study of Denosumab as Adjuvant Treatment for Women With High Risk Early Breast Cancer Receiving Neoadjuvant or Adjuvant Therapy (D-CARE)
A Phase 3 study testing Denosumab in people with Breast Cancer, run by Amgen at 459 sites in 39 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Denosumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4,509 participants
- Where
- 459 sitesin 39 countries
- Study dates
- 2 Jun 2010to 26 Mar 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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:
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
459 sites in 39 countries.
459 sites in 39 countries
United States93 sites
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Abilene, Texas, 79606-5208
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Alhambra, California, 91801
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Anaheim, California, 92801
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Ann Arbor, Michigan, 48109
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Annapolis, Maryland, 21401
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Asheville, North Carolina, 28806
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Athens, Georgia, 30607
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Baltimore, Maryland, 21201
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Bethesda, Maryland, 20817
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Beverly Hills, California, 90211
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Birmingham, Alabama, 35205
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Boston, Massachusetts, 02114
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Boynton Beach, Florida, 33435
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Campbell, California, 95008
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Cedar Rapids, Iowa, 52402
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Charleston, South Carolina, 29414
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Chattanooga, Tennessee, 37404
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Cincinnati, Ohio, 45242
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Columbia, Maryland, 21044
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Columbia, South Carolina, 29210
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Columbus, Ohio, 43210
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Coral Springs, Florida, 33065
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Corpus Christi, Texas, 78463
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Dallas, Texas, 75230-2510
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Dallas, Texas, 75246
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Dallas, Texas, 75390
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Danvers, Massachusetts, 01923
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Denver, Colorado, 80220
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Denville, New Jersey, 07834
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Detroit, Michigan, 48201
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East Setauket, New York, 11733
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Edina, Minnesota, 55435
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El Paso, Texas, 79902
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Fort Lauderdale, Florida, 33316
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Fresno, California, 93720
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Fullerton, California, 92835
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Garland, Texas, 75042
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Germantown, Tennessee, 38138
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Grand Junction, Colorado, 81501
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Hackensack, New Jersey, 07601
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Henderson, Nevada, 89052
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Hershey, Pennsylvania, 17033
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High Point, North Carolina, 27262
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Hilton Head Island, South Carolina, 29926
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Hollywood, Florida, 33021
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Houston, Texas, 77024
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Houston, Texas, 77030
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Hutchinson, Kansas, 67502
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Indianapolis, Indiana, 46260
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Jackson, Mississippi, 39202
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Jacksonville, Florida, 32256
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Jefferson City, Missouri, 65109
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Jonesboro, Arkansas, 72401
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La Verne, California, 91750
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Lancaster, California, 93534
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Lebanon, New Hampshire, 03756-0001
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Lincoln, Nebraska, 68510
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Long Beach, California, 90813
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Los Angeles, California, 90024
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Los Angeles, California, 90025
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Los Angeles, California, 90095-1772
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Melbourne, Florida, 32901
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Minneapolis, Minnesota, 55407
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Nashville, Tennessee, 37203
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New Haven, Connecticut, 06510
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New York, New York, 10003
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New York, New York, 10029
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New York, New York, 10032
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Niles, Illinois, 60714
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Northridge, California, 91328
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Nyack, New York, 10960
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Paducah, Kentucky, 42003
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Pawtucket, Rhode Island, 02860
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Pittsburgh, Pennsylvania, 15213
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Plano, Texas, 75075
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Redondo Beach, California, 90277
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Richlands, Virginia, 24641
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Richmond, Virginia, 23230
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Roanoke, Virginia, 24014
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Saint Louis Park, Minnesota, 55426
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San Antonio, Texas, 78217
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San Antonio, Texas, 78229
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Santa Barbara, California, 93105
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Santa Maria, California, 93454
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Seattle, Washington, 98109-1023
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Seattle, Washington, 98133
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Sioux Falls, South Dakota, 57105
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Tacoma, Washington, 98405
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Torrance, California, 90502
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Tucson, Arizona, 85724
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Tulsa, Oklahoma, 74136
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Tyler, Texas, 75702
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Wichita, Kansas, 67214
Japan28 sites
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Akashi-shi, Hyōgo, 673-8558
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Chuo-ku, Tokyo, 104-0045
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Fukuoka, Fukuoka, 811-1395
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Hidaka-Shi, Saitama, 350-1298
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Isehara-shi, Kanagawa, 259-1193
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Kagoshima, Kagoshima-ken, 892-0833
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Kitaadachi-gun, Saitama, 362-0806
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Kitakyushu-shi, Fukuoka, 802-0077
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Kumamoto, Kumamoto, 860-8556
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Kurashiki-shi, Okayama-ken, 701-0192
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Kure-shi, Hiroshima, 737-0023
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Kurume-shi, Fukuoka, 830-0013
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Kyoto, Kyoto, 606-8507
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Matsuyama, Ehime, 791-0280
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Miyazaki, Miyazaki, 880-0052
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Nagoya, Aichi-ken, 464-8681
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Nagoya, Aichi-ken, 467-8602
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Niigata, Niigata, 951-8566
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Osaka, Osaka, 537-8511
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Osaka, Osaka, 540-0006
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Shimotsuke-shi, Tochigi, 329-0498
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Suita-shi, Osaka, 565-0871
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Suntou-gun, Shizuoka, 411-8777
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Tokyo, 135-8550
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Tokyo, 142-8666
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Tokyo, 160-0023
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Tokyo, 173-0003
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Utsunomiya, Tochigi, 320-0834
Spain24 sites
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A Coruña, Galicia, 15006
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A Coruña, Galicia, 15009
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Alcorcón, Madrid, 28922
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Badalona, Cataluña, 08916
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Barcelona, Cataluña, 08003
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Barcelona, Cataluña, 08035
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Barcelona, Cataluña, 08036
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Barcelona, Cataluña, 08041
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Cádiz, AndalucÃ-a, 11009
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Córdoba, AndalucÃ-a, 14004
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Elche, Valencia, 03203
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Girona, Cataluña, 17007
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Jaén, AndalucÃ-a, 23007
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Lleida, Cataluña, 25198
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Málaga, AndalucÃ-a, 29010
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Madrid, 28009
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Madrid, 28040
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Madrid, 28050
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Sabadell, Cataluña, 08208
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Santander, Cantabria, 39008
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Seville, AndalucÃ-a, 41013
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Valencia, Valencia, 46009
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Valencia, Valencia, 46010
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Zaragoza, Aragón, 50009
Canada22 sites
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Barrie, Ontario, L4M 6M2
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Brampton, Ontario, L6R 3J7
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Calgary, Alberta, T2N 4N2
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Edmonton, Alberta, T6G 1Z2
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Greater Sudbury, Ontario, P3E 5J1
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Greenfield Park, Quebec, J4V 2H1
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Kelowna, British Columbia, V1Y 5L3
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Kingston, Ontario, K7L 5P9
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Kitchener, Ontario, N2G 1G3
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Moncton, New Brunswick, E1C 6Z8
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Montreal, Quebec, H1T 2M4
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Montreal, Quebec, H2W 1T8
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Montreal, Quebec, H3T 1E2
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Ottawa, Ontario, K1H 8L6
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Québec, Quebec, G1S 4L8
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Sault Ste. Marie, Ontario, P6B 0A8
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Sherbrooke, Quebec, J1H 5N4
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St. John's, Newfoundland and Labrador, A1B 3V6
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Sydney, Nova Scotia, B1P 1P3
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Toronto, Ontario, M4C 3E7
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Toronto, Ontario, M9N 1N8
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Victoria, British Columbia, V8R 6V5
Australia20 sites
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Bedford Park, South Australia, 5042
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Bentleigh East, Victoria, 3165
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Camperdown, New South Wales, 2050
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Caringbah, New South Wales, 2229
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East Melbourne, Victoria, 3002
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Fitzroy, Victoria, 3065
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Footscray, Victoria, 3011
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Frankston, Victoria, 3199
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Heidelberg, Victoria, 3084
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Kogarah, New South Wales, 2217
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Malvern, Victoria, 3144
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Parkville, Victoria, 3050
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Perth, Western Australia, 6000
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Richmond, Victoria, 3121
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Ringwood East, Victoria, 3135
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Subiaco, Western Australia, 6008
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Tweed Heads, New South Wales, 2485
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Wahroonga, New South Wales, 2076
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Warrnambool, Victoria, 3280
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Wodonga, Victoria, 3690
Belgium20 sites
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Antwerp, 2020
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Bonheiden, 2820
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Bruges, 8000
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Brussels, 1020
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Brussels, 1090
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Brussels, 1200
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Edegem, 2650
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Ghent, 9000
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Hasselt, 3500
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Kortrijk, 8500
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Leuven, 3000
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Liège, 4000
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Libramont, 6800
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Namur, 5000
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Ostend, 8400
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Ottignies, 1340
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Sint-Niklaas, 9100
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Tournai, 7500
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Wilrijk, 2610
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Yvoir, 5530
United Kingdom19 sites
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Bebington, CH63 4JY
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Birmingham, B15 2TT
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Brighton, BN2 5BE
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Bristol, BS2 8ED
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Cambridge, CB2 0QQ
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Dorset, BH7 7DW
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Guildford, GU2 7XX
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Leeds, LS9 7TF
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London, SW3 6JJ
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London, W2 1NY
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Manchester, M20 4BX
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Manchester, M23 9LT
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Newcastle, NE4 6BE
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Peterborough, PE3 9GZ
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Plymouth, PL6 8DH
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Poole, BH15 2JB
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Portsmouth, PO6 3LY
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Sheffield, S10 2SJ
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Truro, TR1 3LJ
Germany16 sites
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Berlin, 10117
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Berlin, 10713
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Bonn, 53111
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Bottrop, 46236
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Erlangen, 91054
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Frankfurt, 60590
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Kiel, 24105
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Koblenz, 56068
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München, 80335
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München, 80638
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München, 81675
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Mannheim, 68161
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Recklinghausen, 45657
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Rostock, 18059
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Tübingen, 72076
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Trier, 54290
Netherlands16 sites
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Amsterdam, 1066 CX
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Bergen op Zoom, 4624 VT
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Breda, 4819 EV
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Capelle aan den IJssel, 2906 ZC
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Dordrecht, 3318 AT
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Hoofddorp, 2134 TM
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Leiden, 2333 ZA
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Nieuwegein, 3435 CM
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Rotterdam, 3045 PM
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Rotterdam, 3075 EA
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Schiedam, 3118 JH
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Sittard-Geleen, 6162 BG
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The Hague, 2545 CH
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Tiel, 4002 WP
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Tilburg, 5022 GC
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Venlo, 5912 BL
France14 sites
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Angers, 49933
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Bordeaux, 33030
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Dijon, 21079
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Grenoble, 38000
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Hyères, 83400
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Le Mans, 72000
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Lille, 59000
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Monaco, 98012
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Nantes, 44202
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Paris, 75012
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Pierre-Bénite, 69495
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Saint-Priest-en-Jarez, 42270
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Strasbourg, 67091
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Villejuif, 94805
Hungary14 sites
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Budapest, 1032
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Budapest, 1062
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Budapest, 1082
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Budapest, 1122
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Budapest, 1125
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Budapest, 1145
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Debrecen, 4012
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Győr, 9023
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Nyíregyháza, 4400
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Pécs, 7624
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Szeged, 6725
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Székesfehérvár, 8000
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Szolnok, 5004
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Zalaegerszeg, 8900
Brazil13 sites
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Barretos, São Paulo, 14784-400
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Curitiba, Paraná, 81520-060
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ItajaÃ-, Santa Catarina, 88301-220
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Londrina, Paraná, 86050-190
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Porto Alegre, Rio Grande do Sul, 90035-003
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Porto Alegre, Rio Grande do Sul, 90050-170
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Porto Alegre, Rio Grande do Sul, 90610-000
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São Paulo, São Paulo, 01246-000
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São Paulo, São Paulo, 01317-000
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Salvador, Estado de Bahia, 40950-640
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Salvador, Estado de Bahia, 41820-021
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Santo André, São Paulo, 09080-110
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São Paulo, São Paulo, 04038-034
India13 sites
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Ahilyanagar, Maharashtra, 413 736
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Bangalore, Karnataka, 560 054
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Chennai, Tamil Nadu, 600 018
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Chhatrapati Sambhajinagar, Maharashtra, 431 001
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Hyderabad, Andhra Pradesh, 500 024
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Jaipur, Rajasthan, 302 013
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Madurai, Tamil Nadu, 625 107
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Miraj, Maharashtra, 416 410
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Mumbai, Maharashtra, 400 012
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Mumbai, Maharashtra, 400 016
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Nashik, Maharashtra, 422 004
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Nashik, Maharashtra, 422 005
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Pune, Maharashtra, 411 001
Mexico12 sites
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Colima, 28030
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Distrito Federal, 11000
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Durango, 34000
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León, Guanajuato, 37670
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Mexico City, Mexico City, 01120
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Mexico City, Mexico City, 06726
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Mexico City, Mexico City, 07760
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Monterrey, Nuevo León, 64000
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Pachuca, Hidalgo, 42084
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Querétaro, Querétaro, 76178
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San Luis Potosí City, San Luis PotosÃ-, 78200
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Toluca, 50180
Czechia11 sites
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Brno, 625 00
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Brno, 656 53
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Chomutov, 430 12
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Hořovice, 268 31
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Hradec Králové, 500 05
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Olomouc, 775 20
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Prague, 100 00
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Prague, 100 34
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Prague, 140 44
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Prague, 150 06
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Prague, 180 81
Italy11 sites
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Ancona, 60131
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Bari, 70124
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Brescia, 25123
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Meldola FC, 47014
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Milan, 20142
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Monza (MB), 20900
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Palermo, 90100
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Parma, 43100
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San Giovanni Rotondo FG, 71013
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Treviglio (BG), 24047
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Varese, 21100
Israel9 sites
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Ashkelon, 78278
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Haifa, 31096
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Jerusalem, 91031
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Kfar Saba, 44281
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Petah Tikva, 49100
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Poria Eylit, 15208
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Rehovot, 76100
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Tel Aviv, 64239
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Tel Aviv, 69710
Bulgaria7 sites
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Plovdiv, 4004
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Rousse, 7002
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Sofia, 1756
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Sofia, 1784
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Stara Zagora, 6003
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Varna, 9000
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Veliko Tarnovo, 5000
Poland7 sites
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Gdansk, 80-219
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Gdansk, 80-952
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Krakow, 31-108
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Olsztyn, 10-228
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Poznan, 61-485
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Rzeszów, 35-021
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Szczecin, 71-730
Russia7 sites
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Barnaul, 656049
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Chelyabinsk, 454076
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Ivanovo, 153013
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Kazan', 420029
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Moscow, 115478
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Saint Petersburg, 195271
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Saint Petersburg, 197022
Slovakia7 sites
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Bardejov, 085 01
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Košice, 041 91
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Michalovce, 071 01
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Poprad, 058 01
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Prešov, 080 01
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Spišská Nová Ves, 052 01
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Trebišov, 075 01
South Africa7 sites
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Cape Town, 7925
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Groenkloof, Gauteng, 0181
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Johannesburg, Gauteng, 2196
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Pietermaritzburg, 3201
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Port Elizabeth, 6045
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Pretoria, 0002
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Pretoria, 0081
Argentina6 sites
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Neuquén, Neuquén, Q8300HDH
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Provincia de Santa Fe, Santa Fe Province, S3000FFV
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Quilmes, Buenos Aires, B1878DVB
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Quilmes, Buenos Aires, B1878GEG
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San Martín, Buenos Aires, B1650BOB
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San Miguel de Tucumán, Tucumán Province, T4000GTB
Greece6 sites
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Athens, 11522
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Athens, 11528
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Heraklion, 71110
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Pátrai, 26500
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Thessaloniki, 54636
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Thessaloniki, 56429
Ireland6 sites
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Cork
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Dublin, 4
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Dublin, 8
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Dublin, 9
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Limerick
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Waterford
Philippines5 sites
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Cebu City, 6000
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Manila, 1000
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Manila, 1008
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Metro Manila, 1100
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Quezon City, 1102
Portugal5 sites
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Lisbon, 1099-023
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Lisbon, 1500-650
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Porto, 4200-072
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Porto, 4200-319
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Santa Maria da Feira, 4520-211
Romania5 sites
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Bucharest, 022328
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Craiova, 200385
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Sibiu, 550245
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Suceava, 720237
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Timișoara, 300239
South Korea5 sites
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Goyang-si, Gyeonggi-do, 410-769
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Incheon, 405-835
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Seoul, 110-744
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Seoul, 120-752
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Seoul, 135-710
Denmark4 sites
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Ã…rhus C, 8000
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Herning, 7400
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Vejle, 7100
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Viborg, 8800
Malaysia4 sites
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Kota Bharu, Kelantan, 16150
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Kuala Lumpur, Kuala Lumpur, 50703
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Kuala Lumpur, Kuala Lumpur, 56000
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Subang Jaya, Selangor (incl. Putrajaya), 47500
Taiwan4 sites
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Keelung, Keelung, 20401
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Putzu City, Chiayi, 61363
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Tainan, 704
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Taipei, 10002
Turkey (Türkiye)4 sites
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İzmir, 35340
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Ankara, 06100
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Ankara, 06500
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Bornova-Izmir, 35100
Chile3 sites
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Santiago, 8380455
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Temuco, CautÃ-n, 4810469
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Viña del Mar, ValparaÃ-so, 2520612
Latvia3 sites
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Daugavpils, 5417
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Liepāja, 3401
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Riga, 1079
Peru3 sites
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Lima, Lima 11
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Lima, Lima 18
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Lima, Lima 27
About this study
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)
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.
Read the 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:
- 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
- Hormone receptor (estrogen receptor [ER]/progesterone receptor [PR]) status: ER and/or PR positive versus ER and PR negative
- Human epidermal growth factor receptor 2 (HER-2) status: HER-2 positive versus HER-2 negative
- Age: < 50 years versus ≥ 50 years
- 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.
- Conditions
- Breast Cancer
- Being tested
- Placebo, Denosumab
- Keywords
- Early Stage Breast Cancer, Bone Metastasis, Adjuvant treatment, Neoadjuvant treatment, Denosumab, Stage II breast cancer, Stage III breast cancer, Stage IIA breast cancer, Stage IIB breast cancer, Stage IIIA breast cancer, Stage IIIB breast cancer, Stage IIIC breast cancer, Early breast cancer, Breast Tumors, Breast Neoplasms
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Administered subcutaneously for up to 5 years
DenosumabDrug
Also called XGEVA®
Administered subcutaneously for up to 5 years
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
| Denosumab | Experimental | 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. Receives: Drug: Denosumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2010 (estimated)
- Study start2 Jun 2010
- Primary completion31 Aug 2017
- Study completion26 Mar 2018
Why it stopped: Terminated: Amgen decision following Primary Analysis. Not due to safety reason
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 4,509 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01077154
- Sponsor's protocol ID
- 20060359
- Other IDs
- 2009-011299-32, 2009
- Status last verified
- Sep 2021
- First submitted
- 4 Feb 2010
- Last updated
- 28 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 31806543Coleman 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.
PubMed 34185259Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.
PubMed 38979716
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01077154
- Acronym / sponsor ID
- 20060359
- Conditions
- Breast Cancer
- Keywords
- Early Stage Breast Cancer, Bone Metastasis, Adjuvant treatment, Neoadjuvant treatment, Denosumab, Stage II breast cancer, Stage III breast cancer, Stage IIA breast cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated: Amgen decision following Primary Analysis. Not due to safety reason
- Enrolment
- 4,509 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo
- Study start
- 2 Jun 2010 (actual)
- Primary completion
- 31 Aug 2017 (actual)
- Study completion
- 26 Mar 2018 (actual)
- First posted
- 26 Feb 2010 (estimated)
- Results
- Posted 3 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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
- Hormone receptor (estrogen receptor [ER]/progesterone receptor [PR]) status: ER and/or PR positive versus ER and PR negative
- Human epidermal growth factor receptor 2 (HER-2) status: HER-2 positive versus HER-2 negative
- Age: < 50 years versus ≥ 50 years
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboParticipants received placebo subcutaneous injections once every 4 weeks for 6 months followed by placebo subcutaneous injections once every 3 months for 4.5 years. |
| Denosumab | Experimental | Drug: DenosumabParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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:
- 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:
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboAdministered subcutaneously for up to 5 years | Drug | Placebo |
| DenosumabAlso: XGEVA®Administered subcutaneously for up to 5 years | Drug | Denosumab |
Primary outcome
Bone Metastasis-free Survival (BMFS)
Time frame: 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.
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.
4 secondary outcomes
Disease-free Survival (DFS)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31806543Coleman 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.
- Background: PubMed 34185259Coleman 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.
- Derived from this study: PubMed 38979716Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
459 sites in 39 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Denosumab in people with Breast Cancer, run by Amgen at 459 sites in 39 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 459 sites in United States, Japan, Spain, Canada, Australia and 34 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bone Metastasis-free Survival (BMFS) (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01077154, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2021.