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Everolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole (BOLERO-2)

This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals ) Identifier:
First received: March 16, 2009
Last updated: November 25, 2015
Last verified: November 2015
There are no treatments specifically approved after recurrence or progression on a non steroidal aromatase inhibitors (NSAI). In light of the need for new treatment options for postmenopausal women after failure of prior NSAI therapy, the purpose of this Phase III study is to compare efficacy and safety of a treatment with exemestane + everolimus to exemestane + placebo in postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer refractory to NSAI.

Condition Intervention Phase
Breast Cancer
Drug: Everolimus
Drug: Exemestane
Drug: Everolimus Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Double-Blind, Placebo-Controlled Study of Everolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole

Resource links provided by NLM:

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessments. [ Time Frame: date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first ,reported between day of first patient randomized, 27 July 2009, until cut-off date 11 February 2011. ]
    Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST 1.0). For patients with no target lesion, in the absence of new lesions, the overall lesion response at each assessment was one of following: Complete Response CR), Stable Disease SD), Unknown, or Progressive Disease (PD) based on non-target lesion responses. The following is considered progression among patients with lytic or mixed (lytic+sclerotic) bone lesions: appearance of ≥1 new lytic lesions in bone; the appearance of ≥ new lesions outside of bone and unequivocal progression of existing bone lesions.

Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Every 3 months after End of Treatment + 28 days (every 6 weeks before) ]
    Overall survival, the key secondary endpoint in this study, is defined as the time from date of randomization to the date of death due to any cause.

  • Overall Response Rate (ORR) [ Time Frame: Every 6 weeks ]
    ORR is defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST.

  • Incidence of Adverse Events (AEs)/Serious Adverse Events (SAEs) [ Time Frame: Continuous and every 6 weeks ]
    In addition to AEs/SAEs, shift from baseline in vital signs and laboratory results (hematology, blood chemistry) will be reported.

  • Qol Scores ECOG Performance Status [ Time Frame: Every 6 weeks ]
    Change in QoL scores over time and time to deterioration of ECOG performance status.

  • Clinical Benefit Rate (CBR) [ Time Frame: Every 6 weeks ]
    CBR is defined as the proportion of patients whose best overall response is either complete response (CR), a partial response (PR) or stable disease (SD) lasting for at least 24 weeks, according to RECIST.

Enrollment: 724
Study Start Date: June 2009
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus + Exemestane
Everolimus 10 mg daily in combination with exemestane 25 mg daily
Drug: Everolimus
Everolimus was formulated as tablets of 5-mg strength and was packaged into blister packs . Everolimus (two 5 mg tablets daily) were administered in a blinded manner on their respective treatment arms by continuous oral daily dosing.
Other Name: RAD001
Active Comparator: Placebo + Exemestane
Placebo of everolimus in combination with exemestane 25 mg daily
Drug: Exemestane
Exemestane 25 mg orally daily.
Drug: Everolimus Placebo
Placebo was formulated to be indistinguishable from the everolimus tablets. Matching placebo (two tablets daily) were administered in a blinded manner on their respective treatment arms by continuous oral daily dosing.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.
  • Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer
  • Postmenopausal women.
  • Disease refractory to non steroidal aromatase inhibitors (NSAI),
  • Radiological or clinical evidence of recurrence or progression on or after the last systemic therapy prior to randomization.
  • Patients must have at least one lesion that can be accurately measured or bone lesions in the absence of measurable disease as defined above.

Exclusion Criteria:

  • HER2-overexpressing patients
  • Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites etc.).
  • Patients who received more than one chemotherapy line for Advanced Breast Cancer.
  • Previous treatment with exemestane or mTOR inhibitors.
  • Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).
  • Radiotherapy within four weeks prior to randomization
  • Currently receiving hormone replacement therapy,

Other protocol-defined inclusion/exclusion criteria may apply

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Please refer to this study by its identifier: NCT00863655

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United States, Arizona
Ironwood Cancer and Research Centers
Chandler, Arizona, United States, 85224
United States, Arkansas
Highlands Oncology Group DeptofHighlandsOncologyGrp(2)
Fayetteville, Arkansas, United States, 72703
United States, California
Kaiser Permanente Medical Group Kaiser Permanente-Moanalua M.C
Anaheim, California, United States, 92807
Comprehensive Blood and Cancer Center Dept. of CBCC (3)
Bakersfield, California, United States, 93309
Cancer Care Associates Dept.ofCancerCareAssoc. (2)
Fresno, California, United States, 93720
Grass Valley Hematology Oncology Medical Group Dept. of Grass Valley Hem/Onc
Grass Valley, California, United States, 95945
Scripps Clinic SC
La Jolla, California, United States, 92121
The Angeles Clinic and Research Institute
Los Angeles, California, United States, 90025
USC/Kenneth Norris Comprehensive Cancer Center Regulatory Contact 3
Los Angeles, California, United States, 90053
Sharp Memorial Hospital SharpClinicalOncologyResearch
San Diego, California, United States, 92123
University of California San Francisco UCSF Medical Center
San Francisco, California, United States, 94101
Premiere Oncology/Pinnacle Oncology Hematology Dept.ofPremiereOncologyAZ
Santa Monica, California, United States, 90404
St Joseph Heritage Healthcare Dept. of RRMG (4)
Santa Rosa, California, United States, 94503
United States, Florida
Comprehensive Cancer Center - Boca Raton Deerfield Beach
Boca Raton, Florida, United States, 33248
Florida Cancer Research Institute
Davie, Florida, United States, 33328
Florida Cancer Specialists DeptofFloridaCancerSpecialists
Fort Myers, Florida, United States, 33901
Memorial Hospital Memorial Cancer Institute
Hollywood, Florida, United States, 33021
MD Anderson Cancer Center - Orlando Dept.ofMDACC-Orlando(2)
Orlando, Florida, United States, 32806
Palm Beach Cancer Institute
West Palm Beach, Florida, United States, 33401
Florida Medical Clinic PA Dept.ofFloridaMedicalClinic
Zephyrhills, Florida, United States, 33542
United States, Georgia
Georgia Cancer Specialists. Drug Ship
Decatur, Georgia, United States, 30033
United States, Illinois
Rush University Medical Center Study Coordinator
Chicago, Illinois, United States, 60612
Oncology Specialists, SC Dept.of Oncology Specialists
Park Ridge, Illinois, United States, 60068-0736
United States, Indiana
Hematology Oncology of Indiana
Indianapolis, Indiana, United States, 46260
Horizon Oncology Center
Lafayette, Indiana, United States, 47905
United States, Kansas
Cancer Center of Kansas Dept.ofCancerCtr.ofKansas
Wichita, Kansas, United States, 67214-3728
United States, Kentucky
University of Louisville / James Graham Brown Cancer Center SC
Louisville, Kentucky, United States, 40202
United States, Louisiana
Hematology Oncology Clinic Hematology Oncology Clinic (2)
Baton Rouge, Louisiana, United States, 70808
Crescent City Research Consortium, LLC Dept of Hem&Onc Specialist - 2
Metairie, Louisiana, United States, 70006
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Anne Arundel Health System Research Institute Wayson Pavilion
Annapolis, Maryland, United States, 21401
Mercy Medical Center Medical Oncology & Hematology
Baltimore, Maryland, United States, 21202
Weinberg Cancer Institute at Franklin Square Hospital
Baltimore, Maryland, United States, 21237-3998
Maryland Hematology/Oncology Associates, P.A.
Baltimore, Maryland, United States, 21237
Frederick Memorial Hospital Dept. of FMH-IRB
Frederick, Maryland, United States, 21701
Holy Cross Hospital Holy Cross
Silver Spring, Maryland, United States, 20910
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Lahey Clinic Dept of Lahey Clinic (2)
Burlington, Massachusetts, United States, 01805
United States, Minnesota
Fairview Southdale Medical Oncology Clinic
Edina, Minnesota, United States, 55435
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St. Louis Cancer & Breast Institute Dept.ofSt.LouisCancer&Breast
St. Louis, Missouri, United States, 63141
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Southeast Nebraska Oncology Cancer Center
Lincoln, Nebraska, United States, 68510
United States, New Jersey
Regional Cancer Care Associates Dept. of the CCHD
Cherry Hill, New Jersey, United States, 08003
Trinitas Comprehensive Cancer Center Dept. of Trinitas
Elizabeth, New Jersey, United States, 07207
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University of New Mexico Cancer Research Center Dept of UNM Cancer & Research
Albuquerque, New Mexico, United States, 87131
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Clinical Research Alliance Dept.ofArenaOncologyAssoc(2)
Lake Success, New York, United States, 11042
ProHealth Care
Lake Success, New York, United States, 11042
Beth Israel Medical Center Dept.ofBeth Israel Med. Ctr(2)
New York, New York, United States, 10003
Weill Cornell Medical College Weill Cornell Med. Ctr.
New York, New York, United States, 10021
Hematology Oncology Association of Rockland
Nyack, New York, United States, 10960
United States, North Carolina
Marion L. Shepard Cancer Center
Washington, North Carolina, United States, 27889
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Cancer Centers of Southwest Oklahoma Cancer Research Dept.of Southwest Oklahoma
Lawton, Oklahoma, United States, 73505
Cancer Care Associates SC
Tulsa, Oklahoma, United States, 74136
United States, Pennsylvania
Penn State University / Milton S. Hershey Medical Center Division of Oncology (2)
Hershey, Pennsylvania, United States, 17033-0850
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Medical University of South Carolina -Hollings Cancer Center Dept. MUSC/HollingsCancerCtr
Charleston, South Carolina, United States, 29425
United States, Tennessee
Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(5)
Nashville, Tennessee, United States, 37203
United States, Texas
University of Texas Southwestern Medical Center SimmonsComprehensiveCancerCtr.
Dallas, Texas, United States, 75390-8852
The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD(2)
Fort Worth, Texas, United States, 76104
University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(2)
Houston, Texas, United States, 77030-4009
Hope Oncology HOPE Richardson
Richardson, Texas, United States, 75080
United States, Utah
Northern Utah Cancer Associates SC
Ogden, Utah, United States, 84403-3105
Central Utah Clinic CRAD001Y2301
Provo, Utah, United States, 84604
Utah Cancer Specialists Dept.of Utah Cancer Spec. (2)
Salt Lake City, Utah, United States, 84106
University of Utah / Huntsman Cancer Institute Dept.ofHuntsmanCancerInst.(2)
Salt Lake City, Utah, United States, 84112
United States, Virginia
Medical Oncology & Hematology Associates of Northern VA Med. Onc&Hem Assoc. of No.VA
Reston, Virginia, United States, 20190
United States, Wisconsin
University of Wisconsin Hospital & Clinics UW ComprehensiveCancerCtr(2)
Madison, Wisconsin, United States, 53792
Australia, Queensland
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Nambour, Queensland, Australia, 4560
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Redcliffe, Queensland, Australia, 4020
Australia, South Australia
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Bedford Park, South Australia, Australia, 5042
Australia, Victoria
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Parkville, Victoria, Australia, 3050
Australia, Western Australia
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Subiaco, Western Australia, Australia, 6008
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Innsbruck, Austria, A-6020
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Linz, Austria, A-4010
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Salzburg, Austria, 5020
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Wels, Austria, A-4600
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Wien, Austria, A-1090
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Brussel, Belgium, 1090
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Bruxelles, Belgium, 1000
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Leuven, Belgium, 3000
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Liege, Belgium, 4000
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Sint-Niklaas, Belgium, 9100
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Wilrijk, Belgium, 2610
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Salvador, BA, Brazil, 41825-010
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Uberlândia, MG, Brazil, 38408-150
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Rio de Janeiro, RJ, Brazil, 20230-130
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Porto Alegre, RS, Brazil, 90560-030
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São Paulo, SP, Brazil, 01246-000
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Weston, Ontario, Canada, M9N 1N8
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Montreal, Quebec, Canada, H4J 1C5
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Sherbrooke, Quebec, Canada, J1H 5N4
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Quebec, Canada, G1S 4L8
Czech Republic
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Olomouc, CZE, Czech Republic, 775 20
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Brno, Czech Republic, 656 53
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Praha, Czech Republic, 14044
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Alexandria, Egypt
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Cairo, Egypt
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Menoufiya, Egypt
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La Roche sur Yon Cedex, France, 85925
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Le Mans, France, 72000
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Lyon Cedex, France, 69373
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Marseille, France, 13008
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Paris, France, 75010
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Rouen Cedex 1, France, 76038
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Rouen, France, 76000
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Saint-Herblain Cédex, France, 44805
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Saint-Nazaire, France, 44600
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Berlin, Germany, 10098
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Duesseldorf, Germany, 40225
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Frankfurt, Germany, 60389
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Mannheim, Germany, 68165
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Muenchen, Germany, 80637
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Muenchen, Germany, 81377
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Muenster, Germany, 48149
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Trier, Germany, 54290
Hong Kong
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Hong Kong SAR, Hong Kong
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Budapest, Hungary, H-1122
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Szeged, Hungary, H-6720
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Szolnok, Hungary, H-5000
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Brindisi, BR, Italy, 72100
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Catania, CT, Italy, 95100
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Antella - Bagno a Ripoli, FI, Italy, 50011
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Genova, GE, Italy, 16132
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Macerata, MC, Italy, 62100
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Perugia, PG, Italy, 06129
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Torino, TO, Italy, 10126
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Terni, TR, Italy, 05100
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Saronno, Va, Italy, 21047
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Varese, VA, Italy, 21100
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Nagoya, Aichi, Japan, 464-8681
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Kashiwa, Chiba, Japan, 277-8577
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Matsuyama, Ehime, Japan, 791-0280
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Kitakyushu, Fukuoka, Japan, 802-0077
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Maebashi-city, Gunma, Japan, 371-8511
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Sapporo-city, Hokkaido, Japan, 060-8648
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Isehara-city, Kanagawa, Japan, 259-1193
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Kumamoto City, Kumamoto, Japan, 860-8556
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Kyoto-city, Kyoto, Japan, 606-8507
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Suita-city, Osaka, Japan, 565-0871
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Hidaka, Saitama, Japan, 350-1298
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Kitaadachi-gun, Saitama, Japan, 362-0806
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Bunkyo-ku, Tokyo, Japan, 113-8677
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Chuo-ku, Tokyo, Japan, 104-0045
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Chuo-ku, Tokyo, Japan, 104-8560
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Koto, Tokyo, Japan, 135-8550
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Fukuoka, Japan, 811-1395
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Kagoshima, Japan, 892-0833
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Osaka, Japan, 537-8511
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Osaka, Japan, 540-0006
Korea, Republic of
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Hwasun-gun, Jeollanam-do, Korea, Republic of, 519-809
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Seoul, Korea, Korea, Republic of, 03722
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Seoul, Korea, Republic of, 01812
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Alkmaar, Netherlands, 1815 JD
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Amsterdam, Netherlands, 1090 HM
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Den Haag, Netherlands, 2545 CH
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Dordrecht, Netherlands, 3318AT
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Eindhoven, Netherlands, 5631 BM
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Sittard-Geleen, Netherlands, 6162 BG
New Zealand
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Christchurch, New Zealand, 8001
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Lørenskog, Norway, NO-1478
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Krakow, Poland, 31-108
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Rzeszow, Poland, 35-021
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Warszawa, Poland, 04-125
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Malaga, Andalucia, Spain, 29010
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Sevilla, Andalucia, Spain, 41017
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Lleida, Cataluna, Spain, 25198
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Barcelona, Catalunya, Spain, 08035
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Terrassa, Cataluña, Spain, 08221
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La Coruna, Galicia, Spain, 15006
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Santiago de Compostela, Galicia, Spain, 15706
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Mallorca, Islas Baleares, Spain, 07198
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Palma De Mallorca, Islas Baleares, Spain, 07120
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Madrid, Spain, 28033
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Madrid, Spain, 28041
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Madrid, Spain, 28046
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Stockholm, Sweden, SE-118 83
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Stockholm, Sweden, SE-171 76
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Uppsala, Sweden, SE-751 85
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Bangkok, Thailand, 10400
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Bangkok, Thailand, 10700
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Chiang Mai, Thailand, 50200
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Songkla, Thailand, 90110
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Altunizade, Turkey, 34662
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Ankara, Turkey, 06100
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Izmir, Turkey, 35040
United Kingdom
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Broomfield, Chelmsford, United Kingdom, CM1 7ET
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Truro, Cornwall, United Kingdom, TR1 3LJ
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Cardiff, United Kingdom, CF14 2TL
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Nottingham, United Kingdom, NG5 1PB
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Sheffield, United Kingdom, S10 2SJ
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Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):

Responsible Party: Novartis Pharmaceuticals Identifier: NCT00863655     History of Changes
Other Study ID Numbers: CRAD001Y2301
2008-008698-69 ( EudraCT Number )
Study First Received: March 16, 2009
Results First Received: July 31, 2012
Last Updated: November 25, 2015

Keywords provided by Novartis:
Breast Cancer
Estrogen Receptor positive

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Hormones processed this record on April 21, 2017