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

NCT ID: NCT01633060

Last Updated: 2019-01-30

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

432 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-10-03

Study Completion Date

2017-09-21

Brief Summary

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This study was a multicenter, randomized, double-blind, placebo-controlled Phase III study to determine the efficacy and safety of treatment with Buparlisib plus Fulvestrant vs. Placebo plus Fulvestrant in postmenopausal women with hormone Receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative), aromatase inhibitor (AI)-treated, locally advanced or metastatic breast cancer whose disease progressed on or after mammalian target of rapamycin inhibitor (mTORi)-based treatment.

Patients were randomized in 2:1 ratio to treatment with buparlisib 100 mg daily in combination with fulvestrant 500 mg or placebo daily in combination with fulvestrant 500 mg. Randomization was stratified according to visceral disease status (present or absent).

Detailed Description

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Novartis decided not to pursue further development of buparlisib program. On 19 Dec 2016, Novartis notified the Investigators about this decision; accordingly the CBKM120F2303 study was terminated.

Conditions

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Metastatic Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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BKM120 100mg + Fulvestrant

BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.

Group Type EXPERIMENTAL

Fulvestrant

Intervention Type DRUG

Intramuscular fulvestrant 500 mg (Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter)

BKM120

Intervention Type DRUG

BKM120 100 mg once daily

Placebo + Fulvestrant

BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.

Group Type PLACEBO_COMPARATOR

Fulvestrant

Intervention Type DRUG

Intramuscular fulvestrant 500 mg (Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter)

BKM120 matching placebo

Intervention Type DRUG

BKM120 matching placebo, once daily

Interventions

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Fulvestrant

Intramuscular fulvestrant 500 mg (Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter)

Intervention Type DRUG

BKM120

BKM120 100 mg once daily

Intervention Type DRUG

BKM120 matching placebo

BKM120 matching placebo, once daily

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Female patients age 18 years or older
* Histologically and/or cytologically confirmed diagnosis of breast cancer
* Radiologic evidence of inoperable locally advanced or metastatic breast cancer
* Adequate tumor tissue for the analysis of PI3K-related biomarkers
* Human epidermal growth factor receptor-2 (HER2) negative disease, and a known positive hormone receptor status
* Postmenopausal women
* Prior treatment with aromatase inhibitors
* 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
* ECOG performance status ≤ 2

Exclusion Criteria

* Previous treatment with PI3K inhibitors, protein kinase B inhibitors or fulvestrant
* More than one chemotherapy line for metastatic disease
* Hypersensitivity to any of the excipients of buparlisib or fulvestrant
* Symptomatic central nervous system metastases
* Concurrent malignancy or malignancy within 3 years of study enrollment
* Certain drugs or radiation within 2-4 weeks of enrollment
* Increasing or chronic treatment (\>5 days) with corticosteroids or another immunosuppressive agent
* Certain scores on an anxiety and depression mood questionnaire given at screening
* Acute viral hepatitis or a history of chronic or active hepatitis B virus or hepatitis C virus
* Active cardiac disease or a history of cardiac dysfunction
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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University of South Alabama / Mitchell Cancer Institute Univ South AL

Mobile, Alabama, United States

Site Status

Ironwood Cancer and Research Centers SC

Chandler, Arizona, United States

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Highlands Oncology Group

Fayetteville, Arkansas, United States

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Compassionate Cancer Care Medical Group CCCMG

Fountain Valley, California, United States

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Los Angeles Hematology/Oncology Medical Group Onc Dept.

Los Angeles, California, United States

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Cedars Sinai Medical Center SC-5

Los Angeles, California, United States

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University of California at Los Angeles UCLA SC

Los Angeles, California, United States

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Pacific Cancer Care

Monterey, California, United States

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Rocky Mountain Cancer Centers SC

Denver, Colorado, United States

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University Cancer & Blood Center, LLC

Athens, Georgia, United States

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Emory University School of Medicine/Winship Cancer Institute Emory

Atlanta, Georgia, United States

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Moanalua Medical Center. Attn: Oncology Dept

Honolulu, Hawaii, United States

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Edward Hospital Edward Hospital

Naperville, Illinois, United States

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Crescent City Research Consortium, LLC SC

Metairie, Louisiana, United States

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Lsu Health Sciences Center/ Lsu School of Medicine Lsu

New Orleans, Louisiana, United States

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John Ochsner Heart and Vascular Institute Clinical Trials Ochsner 2

New Orleans, Louisiana, United States

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LSU Health Sciences Center Feist-Weiller Cancer Center

New Orleans, Louisiana, United States

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University of Maryland Medical Center Univ Maryland

Baltimore, Maryland, United States

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Mercy Medical Research Institute SC

Manchester, Missouri, United States

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Morristown Memorial Hospital Morristown Mem

Morristown, New Jersey, United States

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CINJ at Cooper University Hospital Dept of Onc

Voorhees Township, New Jersey, United States

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Clinical Research Alliance BKM120F2303

Lake Success, New York, United States

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Clinical Research Alliance

Lake Success, New York, United States

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Montefiore Medical Center Montefiore

The Bronx, New York, United States

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Northwest Cancer Specialists Compass Oncology -BKM

Portland, Oregon, United States

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Oregon Health and Science University SC-5

Portland, Oregon, United States

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University of Pittsburgh Cancer Institute Dept of Magee Women's Hospital

Pittsburgh, Pennsylvania, United States

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The West Clinic Dept. of the West Clinic

Memphis, Tennessee, United States

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Texas Oncology PA Dallas Presbyterian Hospital SC

Dallas, Texas, United States

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Texas Oncology Texas Oncology - Sammons

Dallas, Texas, United States

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Texas Oncology P A SC-Austin

Dallas, Texas, United States

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Texas Oncology P A Texas Oncology - Fort Worth (3

Dallas, Texas, United States

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University of Texas Southwestern Medical Center

Dallas, Texas, United States

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Texas Tech University Health Science Center Dept of Texas Tech

El Paso, Texas, United States

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The Methodist Hospital Cancer Center

Houston, Texas, United States

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US Oncology, P.A.

Tyler, Texas, United States

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Northwest Medical Specialties

Tacoma, Washington, United States

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Novartis Investigative Site

CABA, Buenos Aires, Argentina

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Rosario, Santa Fe Province, Argentina

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San Miguel de Tucumán, Tucumán Province, Argentina

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Rio Negro, Viedma, Argentina

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Innsbruck, Tyrol, Austria

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Linz, , Austria

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Salzburg, , Austria

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Vienna, , Austria

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Brussels, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Namur, , Belgium

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Plovdiv, , Bulgaria

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Vratsa, , Bulgaria

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Bogotá, , Colombia

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Montería, , Colombia

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Tampere, , Finland

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Nice, Alpes Maritimes, France

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Limoges, Haute Vienne, France

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Saint-Cloud, Hauts De Seine, France

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Reims, Marne, France

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Angers, , France

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Clermont-Ferrand, , France

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Lyon, , France

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Saint-Brieuc Cédex, , France

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Saint-Herblain Cédex, , France

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Cologne, North Rhine-Westphalia, Germany

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Berlin, , Germany

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Fulda, , Germany

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Leer, , Germany

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Magdeburg, , Germany

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Mannheim, , Germany

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Mühlhausen, , Germany

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München, , Germany

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München, , Germany

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Ravensburg, , Germany

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Soest, , Germany

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Tübingen, , Germany

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Ulm, , Germany

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Velbert, , Germany

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Marousi, Athens, Greece

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Heraklion Crete, Greece, Greece

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Athens, GR, Greece

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Larissa, GR, Greece

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Patra - RIO, GR, Greece

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Thesaloniki, Thessaloniki, Greece

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Athens, , Greece

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Athens, , Greece

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Budapest, , Hungary

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Budapest, , Hungary

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Szeged, , Hungary

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Szolnok, , Hungary

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L’Aquila, AQ, Italy

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Bari, BA, Italy

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Benevento, BN, Italy

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Brindisi, BR, Italy

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Brescia, BS, Italy

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Monserrato, CA, Italy

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Cremona, CR, Italy

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Catania, CT, Italy

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Meldola, FC, Italy

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Cona, FE, Italy

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Florence, FI, Italy

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Sora, FR, Italy

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Lecco, LC, Italy

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Lecce, LE, Italy

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Monza, MB, Italy

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Macerata, MC, Italy

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Messina, ME, Italy

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Milan, MI, Italy

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Milan, MI, Italy

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Milan, MI, Italy

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Modena, MO, Italy

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Padua, PD, Italy

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Pisa, PI, Italy

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Pordenone, PN, Italy

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Prato, PO, Italy

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Parma, PR, Italy

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Pavia, PV, Italy

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Reggio Calabria, RC, Italy

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Roma, RM, Italy

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Roma, RM, Italy

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Salerno, SA, Italy

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Sassari, SS, Italy

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Candiolo, TO, Italy

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Ivrea, TO, Italy

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Torino, TO, Italy

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Mirano, VE, Italy

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Verona, VR, Italy

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Frattamaggiore, , Italy

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Beirut, , Lebanon

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El Achrafiyé, , Lebanon

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Saida, , Lebanon

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Maastricht, AZ, Netherlands

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Breda, , Netherlands

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Delft, , Netherlands

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Deventer, , Netherlands

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Hoofddorp, , Netherlands

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Leiden, , Netherlands

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Sittard-Geleen, , Netherlands

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Zwolle, , Netherlands

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Bergen, , Norway

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Oslo, , Norway

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Olsztyn, , Poland

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Gyeonggi-do, Korea, South Korea

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Seoul, Korea, South Korea

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Seoul, Korea, South Korea

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Seoul, , South Korea

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Elche, Alicante, Spain

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Jaén, Andalusia, Spain

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Málaga, Andalusia, Spain

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Seville, Andalusia, Spain

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Palma de Mallorca, Balearic Islands, Spain

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Badalona, Catalonia, Spain

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Barcelona, Catalonia, Spain

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Barcelona, Catalonia, Spain

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Barcelona, Catalonia, Spain

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A Coruña, Galicia, Spain

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Santiago de Compostela, Galicia, Spain

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San Cristóbal de La Laguna, Santa Cruz De Tenerife, Spain

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Castellon, Valencia, Spain

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Valencia, Valencia, Spain

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Valencia, Valencia, Spain

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Valencia, Valencia, Spain

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Barcelona, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Santa Cruz de Tenerife, , Spain

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Kalmar, , Sweden

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Stockholm, , Sweden

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Uppsala, , Sweden

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Bangkok, , Thailand

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Blackburn, Lancashire, United Kingdom

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Ipswich, Suffolk, United Kingdom

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Edinburgh, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Nottingham, , United Kingdom

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Countries

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United States Argentina Austria Belgium Bulgaria Canada Colombia Finland France Germany Greece Hungary Italy Lebanon Netherlands Norway Poland South Korea Spain Sweden Thailand United Kingdom

References

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Di Leo A, Johnston S, Lee KS, Ciruelos E, Lonning PE, Janni W, O'Regan R, Mouret-Reynier MA, Kalev D, Egle D, Csoszi T, Bordonaro R, Decker T, Tjan-Heijnen VCG, Blau S, Schirone A, Weber D, El-Hashimy M, Dharan B, Sellami D, Bachelot T. Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer progressing on or after mTOR inhibition (BELLE-3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Jan;19(1):87-100. doi: 10.1016/S1470-2045(17)30688-5. Epub 2017 Dec 7.

Reference Type DERIVED
PMID: 29223745 (View on PubMed)

Other Identifiers

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2012-002571-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CBKM120F2303

Identifier Type: -

Identifier Source: org_study_id

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