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A Phase III Study of BKM120 With Fulvestrant in Patients With HR+,HER2-, AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTORi (BELLE-3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01633060
Recruitment Status : Completed
First Posted : July 4, 2012
Last Update Posted : June 14, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This study will evaluate whether the addition of daily BKM120 to fulvestrant is effective and safe in treating patients with HR+, HER2-, AI treated locally advanced or metastatic breast cancer who progressed on or after mTor inhibitor based treatment.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Fulvestrant Drug: BKM120 Drug: BKM120 matching placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 432 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Double Blind, Placebo Controlled Study of BKM120 With Fulvestrant, in Postmenopausal Women With Hormone Receptor-positive HER2-negative AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTOR Inhibitor Based Treatment
Actual Study Start Date : October 3, 2012
Actual Primary Completion Date : May 23, 2016
Actual Study Completion Date : September 8, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Fulvestrant

Arm Intervention/treatment
Experimental: BKM120 and fulvestrant
BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol test.
Drug: Fulvestrant
Intramuscular fulvestrant 500 mg (cycle 1 days 1 & 15 and once every cycle thereafter)

Drug: BKM120
BKM120 100 mg once daily

Active Comparator: Placebo and fulvestrant
BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Drug: Fulvestrant
Intramuscular fulvestrant 500 mg (cycle 1 days 1 & 15 and once every cycle thereafter)

Drug: BKM120 matching placebo
BKM120 matching placebo, once daily




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Up to approx. 5.5 months ]
    PFS is defined as time from date of randomization to the date of the event, defined as the first radiologically documented disease progression or death due to any cause. PFS is based on local investigator assessment. Patients will be followed up for the duration of the study and for an expected average of every 6 weeks after randomization.


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Up to approx. 21 months ]
    Time from date of randomization to the date of death from any cause. Patients will be followed up for the duration of the study and for an expected average of every 3 months after end of treatment.

  2. Overall response rate (ORR) [ Time Frame: Up to approx. 5.5 months ]
    Proportion of patients, in the full population and by PIK3CA mutational status based on ctDNA, with best overall response of complete response (CR) or partial response (PR). ORR will be assessed according to RECIST 1.1 criteria. Patients will be followed up for the duration of the study and for an expected average of every 6 weeks after randomization.

  3. Clinical benefit rate (CBR) [ Time Frame: Up to approx. 5.5 months ]
    Proportion of patients, in the full population and by PIK3CA mutational status based on ctDNA, with best overall response of complete response (CR) or partial response (PR) or stable disease (SD) or non-CR/non-PD lasting more than 14 weeks. CBR will be assessed according to RECIST 1.1 criteria. Patients will be followed up for the duration of the study and for an expected average of every 6 weeks after randomization.

  4. Type, frequency and severity of adverse events [ Time Frame: at minimum at each study visit and up to approx. 8 months ]
    Safety will be determined by type, frequency and severity of adverse events per CTCAEv4.03 and Type, frequency and severity of laboratory toxicities per CTCAEv4.03. Patients will be followed up for the duration of the study.

  5. Plasma concentration-time profiles of BKM120 - pharmacokinetics (PK) [ Time Frame: C1D1, C1D15, C2D1,C3D1 and C4D1 (a cycle [C] = 4 weeks), D = Day ]
    Plasma concentration-time profiles of BKM120 and appropriate individual PK parameters.

  6. Patient reported outcome for global health status/QoL [ Time Frame: C1D1, C2D15, C4D1, then every 8 weeks until discontinuation (a cycle [C] = 4 weeks). ]
    Time to definitive deterioration in the global health status/QoL scale score. Change from baseline in the global health status/QOL scale score. Patients will be assessed up to approx. 5.5 months.

  7. Progression Free Survival (PFS) in PIK3CA mutational status [ Time Frame: Up to approx. 5.5 months ]
    PFS by PIK3CA mutational status based on ctDNA assessment is defined as time from date of randomization to the date of the event, defined as the first radiologically documented disease progression or death due to any cause. Patient will be followed up to the duration of the study and for an expected avrage of every 6wks after randomization

  8. Overall survival (OS) in PIK3CA mutational status [ Time Frame: Up to approx. 21 months ]
    OS by PIK3CA mutational status based on ctDNA is defined as the time from date of randomization to the date of death from any cause. Patients will be followed up for the duration of the study and for an expected average of every 3 months after end of treatment.



Information from the National Library of Medicine

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

Inclusion Criteria:

  • Postmenopausal women
  • Breast cancer that is locally advanced or metastatic
  • HER2 negative disease, and a known positive hormone receptor status (common breast cancer classification tests)
  • A tumor sample must be shipped to a central lab for identification of biomarkers (PI3K activation status) before randomization
  • Prior treatment with AIs
  • Evidence of progression to the combination of mTORi and endocrine therapy given as the last therapy prior to study entry
  • Adequate bone marrow and organ function

Exclusion Criteria:

  • More than 1 prior chemotherapy given for locally advanced or metastatic disease
  • Previous treatment with PI3K inhibitors, AKT inhibitors or fulvestrant
  • Symptomatic CNS metastases
  • Concurrent malignancy or malignancy within 3 years prior to start of study treatment
  • Certain drugs or radiation within 2-4 weeks of enrollment
  • Increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent
  • Active heart (cardiac) disease or a history of cardiac dysfunction as defined in the protocol
  • Hyper sensitivity to fulvestrant treatment excipients
  • Certain scores on an anxiety and depression mood questionnaire given at screening
  • Acute viral hepatitis or history of chronic or acute HBV, HCV, HAV, HDV, HEV
  • Other protocol defined criteria may apply

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01633060


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Locations
United States, Alabama
University of South Alabama / Mitchell Cancer Institute Univ South AL
Mobile, Alabama, United States, 36688
United States, Arizona
Ironwood Cancer and Research Centers SC
Chandler, Arizona, United States, 85224
United States, Arkansas
Highlands Oncology Group Dept of Highlands Oncology Grp
Fayetteville, Arkansas, United States, 72703
United States, California
Compassionate Cancer Care Medical Group CCCMG
Fountain Valley, California, United States, 92708
Los Angeles Hematology/Oncology Medical Group Onc Dept.
Los Angeles, California, United States, 90017
Cedars Sinai Medical Center SC-5
Los Angeles, California, United States, 90048
University of California at Los Angeles UCLA SC
Los Angeles, California, United States, 90095
Pacific Cancer Care
Monterey, California, United States, 93940
United States, Colorado
Rocky Mountain Cancer Centers SC
Denver, Colorado, United States, 80218
United States, Georgia
University Cancer & Blood Center, LLC
Athens, Georgia, United States, 30607
Emory University School of Medicine/Winship Cancer Institute Emory
Atlanta, Georgia, United States, 30322
United States, Hawaii
Moanalua Medical Center. Attn: Oncology Dept
Honolulu, Hawaii, United States, 96817
United States, Illinois
Edward Hospital Edward Hospital
Naperville, Illinois, United States, 60540
United States, Louisiana
Crescent City Research Consortium, LLC SC
Metairie, Louisiana, United States, 70006
Lsu Health Sciences Center/ Lsu School of Medicine Lsu
New Orleans, Louisiana, United States, 70115
John Ochsner Heart & Vascular Institute Clinical Trials Ochsner 2
New Orleans, Louisiana, United States, 70121
LSU Health Sciences Center Feist-Weiller Cancer Center
New Orleans, Louisiana, United States, 70122-2822
United States, Maryland
University of Maryland Medical Center Univ Maryland
Baltimore, Maryland, United States, 21201
United States, Missouri
Mercy Medical Research Institute SC
Manchester, Missouri, United States, 63021
United States, New Jersey
Morristown Memorial Hospital Morristown Mem
Morristown, New Jersey, United States, 07962
CINJ at Cooper University Hospital Dept of Onc
Voorhees, New Jersey, United States, 08043
United States, New York
Montefiore Medical Center Montefiore
Bronx, New York, United States, 10467
Clinical Research Alliance BKM120F2303
Lake Success, New York, United States, 11042
Clinical Research Alliance
Lake Success, New York, United States, 11042
United States, Oregon
Northwest Cancer Specialists Compass Oncology -BKM
Portland, Oregon, United States, 97210
Oregon Health & Science University SC-5
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pittsburgh Cancer Institute Dept of Magee Women's Hospital
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
The West Clinic Dept. of the West Clinic
Memphis, Tennessee, United States, 38120
United States, Texas
Texas Oncology PA Dallas Presbyterian Hospital SC
Dallas, Texas, United States, 75231
Texas Oncology Texas Oncology - Sammons
Dallas, Texas, United States, 75246
Texas Oncology SC-Austin
Dallas, Texas, United States, 75251
Texas Oncology Texas Oncology - Fort Worth (3
Dallas, Texas, United States, 75251
University of Texas Southwestern Medical Center UT Southwestern 2
Dallas, Texas, United States, 75390
Texas Tech University Health Science Center Dept of Texas Tech
El Paso, Texas, United States, 79905
The Methodist Hospital Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Northwest Medical Specialties
Tacoma, Washington, United States, 98405
Argentina
Novartis Investigative Site
Caba, Buenos Aires, Argentina, C1050AAK
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Rosario, Santa Fe, Argentina, S2000KZE
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San Miguel De Tucuman, Tucuman, Argentina, T4000IAK
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Rio Negro, Viedma, Argentina, 8500
Austria
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Innsbruck, Tyrol, Austria, 6020
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Linz, Austria, 4010
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Salzburg, Austria, 5020
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Wien, Austria, A-1090
Belgium
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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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Namur, Belgium, 5000
Bulgaria
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Plovdiv, Bulgaria, 4000
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Plovdiv, Bulgaria, 4004
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Sofia, Bulgaria, 1303
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Sofia, Bulgaria, 1527
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Sofia, Bulgaria, 1756
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Varna, Bulgaria, 9010
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Vratsa, Bulgaria, 3000
Canada, Quebec
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Montreal, Quebec, Canada, H2W 1T8
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Montreal, Quebec, Canada, H3A 1A1
Colombia
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Bogota, Colombia
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Monteria, Colombia
Finland
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Tampere, Finland, FIN-33521
France
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Limoges cedex, Haute Vienne, France, 87000
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Saint-Cloud, Hauts De Seine, France, 92210
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Reims Cedex, Marne, France, 51056
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Angers Cedex 02, France, 49055
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Clermont-Ferrand, France, 63011
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Lyon Cedex, France, 69373
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Nice Cedex 2, France, 06189
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Paris, France, 75231
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Rouen Cedex 1, France, 76038
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Saint-Brieuc Cédex, France, 22015
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Saint-Herblain Cédex, France, 44805
Germany
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Koeln, Nordrhein-Westfalen, Germany, 50937
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Berlin, Germany, 12203
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Bonn, Germany, 53111
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Dresden, Germany, 01307
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Erlangen, Germany, 91054
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Essen, Germany, 45136
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Essen, Germany, 45147
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Frankfurt, Germany, 60389
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Fulda, Germany, 36043
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Karlsruhe, Germany, 76135
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Kiel, Germany, 24103
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Leer, Germany, 26789
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Magdeburg, Germany, 39120
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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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Mühlhausen, Germany, 99974
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Ravensburg, Germany, 88214
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Soest, Germany, 59494
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Tuebingen, Germany, 72076
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Ulm, Germany, 89081
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Velbert, Germany, 42551
Greece
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Marousi, Athens, Greece, 15123
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Athens, GR, Greece, 151 23
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Larissa, GR, Greece, 411 10
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Patra - RIO, GR, Greece, 265 04
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Thesaloniki, Thessaloniki, Greece, 54622
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Athens, Greece, 18547
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Athens, Greece, GR-115 22
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Heraklion Crete, Greece, 711 10
Hungary
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Budapest, Hungary, 1134
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Budapest, Hungary, H-1122
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Szeged, Hungary, H-6720
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Szolnok, Hungary, H-5000
Italy
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L'Aquila, AQ, Italy, 67100
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Bari, BA, Italy, 70124
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Benevento, BN, Italy, 82100
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Brindisi, BR, Italy, 72100
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Brescia, BS, Italy, 25123
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Monserrato, CA, Italy, 09042
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Cremona, CR, Italy, 26100
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Catania, CT, Italy, 95100
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Meldola, FC, Italy, 47014
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Cona, FE, Italy, 44100
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Firenze, FI, Italy, 50134
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Sora, FR, Italy, 03039
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Lecco, LC, Italy, 23900
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Lecce, LE, Italy, 73100
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Monza, MB, Italy, 20900
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Macerata, MC, Italy, 62100
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Messina, ME, Italy, 98158
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Milano, MI, Italy, 20121
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Milano, MI, Italy, 20132
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Milano, MI, Italy, 20141
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Modena, MO, Italy, 41124
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Padova, PD, Italy, 35100
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Pisa, PI, Italy, 56126
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Pordenone, PN, Italy, 33170
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Prato, PO, Italy, 59100
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Parma, PR, Italy, 43100
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Pavia, PV, Italy, 27100
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Reggio Calabria, RC, Italy, 89124
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Roma, RM, Italy, 00128
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Roma, RM, Italy, 00168
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Salerno, SA, Italy, 84131
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Sassari, SS, Italy, 07100
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Candiolo, TO, Italy, 10060
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Ivrea, TO, Italy, 10015
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Torino, TO, Italy, 10126
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Mirano, VE, Italy, 30035
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Verona, VR, Italy, 37126
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Frattamaggiore, Italy, 80020
Korea, Republic of
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Gyeonggi-do, Korea, Korea, Republic of, 10408
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Seoul, Korea, Korea, Republic of, 03080
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Seoul, Korea, Korea, Republic of, 05505
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Seoul, Korea, Republic of, 03722
Lebanon
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Beirut, Lebanon, 166830
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Beirut, Lebanon
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Saida, Lebanon, 652
Netherlands
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Breda, Netherlands, 4819 EV
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Delft, Netherlands, NL 2625 AD
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Deventer, Netherlands, 7416 SE
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Hoofddorp, Netherlands, 2134 TM
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Leiden, Netherlands, 2300 RC
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Maastricht, Netherlands, 5800
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Sittard-Geleen, Netherlands, 6162 BG
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Zwolle, Netherlands, 8025 AB
Norway
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Bergen, Norway, 5021
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Oslo, Norway, NO-0450
Poland
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Konin, Poland, 62-500
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Olsztyn, Poland, 10226
Spain
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Elche, Alicante, Spain, 03203
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Jaen, Andalucia, Spain, 23007
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Malaga, Andalucia, Spain, 29010
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Sevilla, Andalucia, Spain, 41009
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Badalona, Catalunya, Spain, 08916
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Barcelona, Catalunya, Spain, 08003
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Barcelona, Catalunya, Spain, 08035
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Barcelona, Catalunya, Spain, 08036
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Castellon, Comunidad Valenciana, Spain, 12002
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Valencia, Comunidad Valenciana, Spain, 46009
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Valencia, Comunidad Valenciana, Spain, 46010
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Valencia, Comunidad Valenciana, Spain, 46014
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La Coruna, Galicia, Spain, 15006
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Santiago de Compostela, Galicia, Spain, 15706
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Palma De Mallorca, Islas Baleares, Spain, 07120
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Majadahonda, Madrid, Spain, 28222
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La Laguna, Santa Cruz De Tenerife, Spain, 38320
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Barcelona, Spain, 08041
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Madrid, Spain, 28007
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Madrid, Spain, 28034
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Madrid, Spain, 28040
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Madrid, Spain, 28041
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Madrid, Spain, 28046
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Santa Cruz de Tenerife, Spain, 38009
Sweden
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Kalmar, Sweden, SE-391 85
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Stockholm, Sweden, SE-171 76
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Uppsala, Sweden, 751 85
Thailand
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Bangkok, Thailand, 10400
United Kingdom
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Blackburn, Lancashire, United Kingdom, BB2 3HH
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Ipswich, Suffolk, United Kingdom, IP4 5PD
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Edinburgh, United Kingdom, EH4 2XU
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London, United Kingdom, SM2 5PT
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London, United Kingdom, SW3 6JJ
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Manchester, United Kingdom, M20 2BX
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Nottingham, United Kingdom, NG5 1PB
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01633060     History of Changes
Other Study ID Numbers: CBKM120F2303
2012-002571-34 ( EudraCT Number )
First Posted: July 4, 2012    Key Record Dates
Last Update Posted: June 14, 2018
Last Verified: June 2018

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
BKM120
fulvestrant
breast cancer
metastatic
locally advanced
AI treated
mTOR inhibitor
PI3K
PIK3CA
PTEN
HER2-
HR+

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Everolimus
Sirolimus
Estradiol
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Estrogens
Hormones
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents