Phase III Study of BKM120/Placebo With Fulvestrant in Postmenopausal Patients With Hormone Receptor Positive HER2-negative Locally Advanced or Metastatic Breast Cancer Refractory to Aromatase Inhibitor

NCT ID: NCT01610284

Last Updated: 2020-08-25

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

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1147 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-08-07

Study Completion Date

2019-04-19

Brief Summary

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This study was a multi-center, randomized, double-blind, placebo controlled Phase III study to determine the efficacy and safety of treatment with buparlisib plus fulvestrant versus fulvestrant plus placebo in postmenopausal women with hormone Receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative), locally advanced or metastatic breast cancer (MBC) whose disease has progressed on or after aromatase inhibitor (AI) treatment.

Detailed Description

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Patients were randomized (1:1) to receive buparlisib (100 mg/day) or placebo with fulvestrant (500 mg); randomization was stratified by PI3K pathway activation status (activated, non-activated, unknown determined in archival tumor tissue) and visceral disease status (present or absent). Tumor evaluation was performed 6 weeks after the randomization date and then every 8 weeks until radiological progression (based on Response Evaluation Criteria In Solid Tumors \[RECIST\] version 1.1).

Novartis made the decision not to pursue further development of buparlisib and to terminate the ongoing studies in the program. Accordingly, on 19-Dec-2016, Novartis notified all the Investigators about the decision not to pursue further development of buparlisib in Breast Cancer. As a result, the CBKM120F2302 study was terminated on 19-Apr-2019 (last subject last visit).

Conditions

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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

* Locally advanced or metastatic breast cancer
* HER2-negative and hormone receptor-positive status (common breast cancer classification tests)
* Postmenopausal woman
* A tumor sample must be shipped to a Novartis designated laboratory for identification of biomarkers (PI3K activation status)
* Progression or recurrence of breast cancer while on or after aromatase inhibitor treatment
* Measurable disease or non measurable disease bone lesions in the absence of measurable disease as per RECIST 1.1
* Adequate bone marrow and organ function defined by laboratory values

Exclusion Criteria

* Previous treatment with PI3K inhibitors, AKT inhibitors, mTOR inhibitor or fulvestrant
* More than one prior chemotherapy line for metastatic disease
* Symptomatic brain metastases
* Increasing or chronic treatment (\> 5 days) with corticosteroids or another immunosuppressive agent
* Active heart (cardiac) disease as defined in the protocol
* Certain scores on an anxiety and depression mood questionnaires
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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Novartis Investigative Site

Valencia, Valencia, Spain

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Novartis Investigative Site

Valencia, Valencia, Spain

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Novartis Investigative Site

Valencia, Valencia, Spain

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Novartis Investigative Site

Barcelona, , Spain

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Novartis Investigative Site

Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Novartis Investigative Site

Madrid, , Spain

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University of South Alabama / Mitchell Cancer Institute Deptof Mitchell Cancer Inst(2)

Mobile, Alabama, United States

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Arizona Oncology Associates Dept of Oncology

Phoenix, Arizona, United States

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Highlands Oncology Group

Fayetteville, Arkansas, United States

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Shapiro and Stafford and Yee and Polanski Study Coordinator

Arcadia, California, United States

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Cancer Care Associates Dept.ofCancerCareAssoc.

Fresno, California, United States

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St. Jude Heritage Medical Group Virginia Crosson Cancer Center

Fullerton, California, United States

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University of California San Diego - Moores Cancer Center UCSD 3

La Jolla, California, United States

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Los Angeles Hematology/Oncology Medical Group LA Cancer Network

Los Angeles, California, United States

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USC Kenneth Norris Comprehensive Cancer Center Dept.ofNorrisCompCancerCtr (3)

Los Angeles, California, United States

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University of California at Los Angeles Dept. of UCLA

Los Angeles, California, United States

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Ventura County Hematology and Oncology PMK Medical Group

Oxnard, California, United States

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Coastal Integrative Cancer Care

San Luis Obispo, California, United States

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Santa Barbara Hematolgy Oncology Medical Group

Santa Barbara, California, United States

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Central Coast Medical Oncology Corporation

Santa Maria, California, United States

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St Joseph Heritage Healthcare Dept. of RRMG (4)

Santa Rosa, California, United States

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Granada Hills Cancer Center

Valencia, California, United States

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Kaiser Permanente Northwest Kaiser

Denver, Colorado, United States

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Rocky Mountain Cancer Centers RMCC

Greenwood Village, Colorado, United States

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Memorial Regional Cancer Center MRCC

Hollywood, Florida, United States

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Cancer Specialists of North Florida SC - F2302

Jacksonville, Florida, United States

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University of Miami Univ Miami 2

Miami, Florida, United States

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MD Anderson Cancer Center - Orlando MD Orlando

Orlando, Florida, United States

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Georgia Cancer Specialists SC

Decatur, Georgia, United States

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North Shore University Health System

Evanston, Illinois, United States

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Cadence Health

Geneva, Illinois, United States

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Cancer Care and Hematology Specialists of Chicagoland Niles

Multiple Locations, Illinois, United States

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Cancer Center of Kansas CCK

Wichita, Kansas, United States

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Mercy Medical Center Mercy Medical SC

Baltimore, Maryland, United States

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Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Med Sidney/John Hopkins

Baltimore, Maryland, United States

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Frederick Memorial Hospital Fred. Mem. Hosp.

Frederick, Maryland, United States

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Maryland Oncology Hematology, P.A. SC

Rockville, Maryland, United States

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Massachusetts General Hospital SC

Boston, Massachusetts, United States

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West Michigan Cancer Center Dept of Oncology

Kalamazoo, Michigan, United States

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Hematology and Oncology Association at Bridgepoint Hem Onc Bridgepoint

Tupelo, Mississippi, United States

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Washington University School of Medicine Regulatory

St Louis, Missouri, United States

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Hackensack Meridian Health

Brick, New Jersey, United States

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The Valley Hospital / Luckow Pavillion

Paramus, New Jersey, United States

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Clinical Research Alliance SC-2

Lake Success, New York, United States

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Memorial Sloan Kettering Dept Onc

New York, New York, United States

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University of Rochester Medical Center Univ Rochester

Rochester, New York, United States

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Levine Cancer Institute Levine Cancer Institute

Charlotte, North Carolina, United States

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Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

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Case Western Reserve SC

Cleveland, Ohio, United States

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Northwest Cancer Specialists Portland Loc

Portland, Oregon, United States

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St. Luke's Hospital and Health Network St Luke's (2)

Bethlehem, Pennsylvania, United States

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Charleston Hematology Oncology Association PA

Charleston, South Carolina, United States

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Tennessee Cancer Specialists

Knoxville, Tennessee, United States

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Vanderbilt University Medical Center Vanderbilt - Thompson Ln

Nashville, Tennessee, United States

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Texas Oncology P A Midtown

Dallas, Texas, United States

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Texas Oncology P A TX Onc - Bedford

Dallas, Texas, United States

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Texas Oncology P A TX Onc - Med City Dallas

Dallas, Texas, United States

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Texas Oncology P A TX Onc - Southwest

Dallas, Texas, United States

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Oncology Consultants Oncology Consultants, P.A.

Houston, Texas, United States

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Cancer Therapy and Research Center UT Health Science Center Institute for Drug Development

San Antonio, Texas, United States

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Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)

Salt Lake City, Utah, United States

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Oncology Hematology Associates of Southeast Virginia Salem VA Branch

Roanoke, Virginia, United States

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Kadlec Clinic Hematology and Oncology Kadlec Clinic Hematology & Onc

Kennewick, Washington, United States

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West Virginia University/ Mary Babb Randolph Cancer Center Dept of Oncology

Morgantown, West Virginia, United States

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Cancer TEAM Bellin Health Belin Health

Green Bay, Wisconsin, United States

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Dean Health System Dean Hematology Oncology

Madison, Wisconsin, United States

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University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc 3

Madison, Wisconsin, United States

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Novartis Investigative Site

CABA, Buenos Aires, Argentina

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Mar del Plata, Buenos Aires, Argentina

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San Miguel de Tucumán, Tucumán Province, Argentina

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Rio Negro, Viedma, Argentina

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Sydney, New South Wales, Australia

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Woollongong, New South Wales, Australia

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South Brisbane, Queensland, Australia

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Clayton, Victoria, Australia

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Melbourne, Victoria, Australia

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Murdoch, Western Australia, Australia

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Nedlands, Western Australia, Australia

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Linz, , Austria

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Salzburg, , Austria

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Vienna, , Austria

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Jette, Brussels Capital, Belgium

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Brussels, , Belgium

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Charleroi, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Namur, , Belgium

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Wilrijk, , Belgium

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Belo Horizonte, Minas Gerais, Brazil

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Curitiba, Paraná, Brazil

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Natal, Rio Grande do Norte, Brazil

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Ijuí, Rio Grande do Sul, Brazil

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Barretos, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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Sorocaba, São Paulo, Brazil

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Kelowna, British Columbia, Canada

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Vancouver, British Columbia, Canada

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Halifax, Nova Scotia, Canada

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Cambridge, Ontario, Canada

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London, Ontario, Canada

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Newmarket, Ontario, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Laval, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Regina, Saskatchewan, Canada

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Harbin, Heilongjiang, China

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Changsha, Hunan, China

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Nanjing, Jiangsu, China

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Shengyang, Liaoning, China

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Shanghai, Shanghai Municipality, China

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Chengdu, Sichuan, China

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Hangzhou, Zhejiang, China

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Beijing, , China

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Guangzhou, , China

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Shanghai, , China

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Brno Bohunice, Czech Republic, Czechia

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Olomouc, CZE, Czechia

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Brno, , Czechia

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Nice, Alpes Maritimes, France

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Dijon, Cote D Or, France

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Saint Priest En Jarez, Pays de la Loire Region, France

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Angers, , France

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Avignon, , France

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Besançon, , France

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Bordeaux, , France

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Caen, , France

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Clermont-Ferrand, , France

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Le Mans, , France

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Lille, , France

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Montpellier, , France

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Paris, , France

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Paris, , France

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Rouen, , France

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Saint-Herblain Cédex, , France

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Strasbourg, , France

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Toulouse, , France

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Villejuif, , France

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Langen, Hesse, Germany

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Recklinghausen, North Rhine-Westphalia, Germany

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Lübeck, Schleswig-Holstein, Germany

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Essen, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Heidelberg, , Germany

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Kiel, , Germany

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Magdeburg, , Germany

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Mainz, , Germany

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Mannheim, , Germany

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Mühlhausen, , Germany

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München, , Germany

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Saarbrücken, , Germany

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Velbert, , Germany

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Würzburg, , Germany

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Heraklion Crete, Greece, Greece

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Thessaloniki, GR, Greece

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Athens, , Greece

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Pátrai, , Greece

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Budapest, , Hungary

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Debrecen, , Hungary

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Miskolc, , Hungary

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Szolnok, , Hungary

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Haifa, , Israel

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Jerusalem, , Israel

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Petah Tikva, , Israel

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Ramat Gan, , Israel

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Tel Aviv, , Israel

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Cuneo, CN, Italy

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Cremona, CR, Italy

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Catanzaro, CZ, Italy

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Meldola, FC, Italy

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Florence, FI, Italy

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Lido di Camaiore, LU, Italy

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Macerata, MC, 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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Milan, MI, Italy

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Rozzano, MI, Italy

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Pisa, PI, Italy

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Aviano, PN, Italy

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Roma, RM, Italy

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Roma, RM, Italy

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Roma, RM, Italy

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Rimini, RN, Italy

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Torino, TO, Italy

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Mirano, VE, Italy

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Bologna, , Italy

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Napoli, , Italy

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Nagoya, Aichi-ken, Japan

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Kashiwa, Chiba, Japan

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Fukuoka, Fukuoka, Japan

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Maebashi, Gunma, Japan

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Sapporo, Hokkaido, Japan

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Isehara, Kanagawa, Japan

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Yokohama, Kanagawa, Japan

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Kumamoto, Kumamoto, Japan

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Sakyo Ku, Kyoto, Japan

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Osaka, Osaka, Japan

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Osaka, Osaka, Japan

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Suita, Osaka, Japan

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Koto Ku, Tokyo, Japan

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Nijmegen, , Netherlands

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Surquillo, Lima region, Peru

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Krakow, , Poland

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Olsztyn, , Poland

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Warsaw, , Poland

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Moscow, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Singapore, , Singapore

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Bratislava, Slovak Republic, Slovakia

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Košice, , Slovakia

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Johannesburg, , South Africa

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Parktown, , South Africa

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Suwon, Gyeonggi-do, South Korea

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Seoul, Seocho Gu, South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Elche, Alicante, Spain

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Córdoba, Andalusia, 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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Seville, Andalusia, Spain

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Seville, Andalusia, Spain

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Toledo, Castille-La Mancha, 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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Barcelona, Catalonia, Spain

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Tarragona, Catalonia, Spain

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Las Palmas de Gran Canarias, Las Palmas de Gran Canaria, Spain

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San Sebastián de los Reyes, Madrid, Spain

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El Palmar, Murcia, Spain

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Oviedo, Principality of Asturias, Spain

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Madrid, , Spain

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Madrid, , Spain

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Zaragoza, , Spain

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Bellinzona, , Switzerland

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Geneva, , Switzerland

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Zurich, , Switzerland

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Kaohsiung City, , Taiwan

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Bangkok, , Thailand

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Bangkok, , Thailand

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Bangkok, , Thailand

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Truro, Cornwall, United Kingdom

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Bournemouth, , United Kingdom

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Derby, , United Kingdom

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Leicester, , United Kingdom

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Liverpool, , 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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Oxford, , United Kingdom

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Countries

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United States Argentina Australia Austria Belgium Brazil Canada China Czechia France Germany Greece Hungary Israel Italy Japan Netherlands Peru Poland Russia Singapore Slovakia South Africa South Korea Spain Switzerland Taiwan Thailand United Kingdom

References

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Campone M, Im SA, Iwata H, Clemons M, Ito Y, Awada A, Chia S, Jagiello-Gruszfeld A, Pistilli B, Tseng LM, Hurvitz S, Masuda N, Cortes J, De Laurentiis M, Arteaga CL, Jiang Z, Jonat W, Le Mouhaer S, Sankaran B, Bourdeau L, El-Hashimy M, Sellami D, Baselga J. Buparlisib plus fulvestrant versus placebo plus fulvestrant for postmenopausal, hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer: Overall survival results from BELLE-2. Eur J Cancer. 2018 Nov;103:147-154. doi: 10.1016/j.ejca.2018.08.002. Epub 2018 Sep 18.

Reference Type DERIVED
PMID: 30241001 (View on PubMed)

Baselga J, Im SA, Iwata H, Cortes J, De Laurentiis M, Jiang Z, Arteaga CL, Jonat W, Clemons M, Ito Y, Awada A, Chia S, Jagiello-Gruszfeld A, Pistilli B, Tseng LM, Hurvitz S, Masuda N, Takahashi M, Vuylsteke P, Hachemi S, Dharan B, Di Tomaso E, Urban P, Massacesi C, Campone M. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Jul;18(7):904-916. doi: 10.1016/S1470-2045(17)30376-5. Epub 2017 May 30.

Reference Type DERIVED
PMID: 28576675 (View on PubMed)

Other Identifiers

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2011-005524-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CBKM120F2302

Identifier Type: -

Identifier Source: org_study_id

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