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 (BELLE-2)

A Phase III Randomized, Double Blind Placebo Controlled Study of BKM120 With Fulvestrant, in Postmenopausal Women With Hormone Receptor-positive HER2-negative Locally Advanced or Metastatic Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Fulvestrant; Drug: BKM120; Drug: BKM120 matching placebo

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 1147
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1050AAK
      • Novartis Investigative Site
    • Mar del Plata, Buenos Aires, Argentina, B7600CTO
      • Novartis Investigative Site
  • Tucuman
    • San Miguel De Tucuman, Tucuman, Argentina, T4000IAK
      • Novartis Investigative Site
  • Viedma
    • Rio Negro, Viedma, Argentina, 8500
      • Novartis Investigative Site
• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2060
      • Novartis Investigative Site
    • Woollongong, New South Wales, Australia, 2500
      • Novartis Investigative Site
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Novartis Investigative Site
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Novartis Investigative Site
    • Melbourne, Victoria, Australia, 3000
      • Novartis Investigative Site
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Novartis Investigative Site
    • Nedlands, Western Australia, Australia, 6009
      • Novartis Investigative Site
• Austria
  • Linz, Austria, 4010
    • Novartis Investigative Site
  • Salzburg, Austria, 5020
    • Novartis Investigative Site
  • Wien, Austria, A-1090
    • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1000
    • Novartis Investigative Site
  • Charleroi, Belgium, 6000
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
  • Liege, Belgium, 4000
    • Novartis Investigative Site
  • Namur, Belgium, 5000
    • Novartis Investigative Site
  • Wilrijk, Belgium, 2610
    • Novartis Investigative Site
  • Brussel
    • Jette, Brussel, Belgium, 1090
      • Novartis Investigative Site
• Brazil
  • MG
    • Belo Horizonte, MG, Brazil, 30150-270
      • Novartis Investigative Site
  • PR
    • Curitiba, PR, Brazil, 81520-060
      • Novartis Investigative Site
  • RN
    • Natal, RN, Brazil, 59075 740
      • Novartis Investigative Site
  • RS
    • Ijuí, RS, Brazil, 98700-000
      • Novartis Investigative Site
  • SP
    • Barretos, SP, Brazil, 14784 400
      • Novartis Investigative Site
    • Sao Paulo, SP, Brazil, 01246 000
      • Novartis Investigative Site
    • Sorocaba, SP, Brazil
      • Novartis Investigative Site
• Canada
  • Quebec, Canada, G1S 4L8
    • Novartis Investigative Site
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Novartis Investigative Site
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Novartis Investigative Site
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • Novartis Investigative Site
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Novartis Investigative Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Novartis Investigative Site
  • Ontario
    • Cambridge, Ontario, Canada, N1R 3G2
      • Novartis Investigative Site
    • London, Ontario, Canada, N6A 4L6
      • Novartis Investigative Site
    • Newmarket, Ontario, Canada, J7Y 2P9
      • Novartis Investigative Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Novartis Investigative Site
  • Quebec
    • Laval, Quebec, Canada, H7M 3L9
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H2L 4M1
      • Novartis Investigative Site
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Novartis Investigative Site
• China
  • Beijing, China, 100039
    • Novartis Investigative Site
  • Guangzhou, China, 510060
    • Novartis Investigative Site
  • Shanghai, China, 200025
    • Novartis Investigative Site
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Novartis Investigative Site
  • Hunan
    • Changsha, Hunan, China, 410013
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Novartis Investigative Site
  • Liaoning
    • Shengyang, Liaoning, China, 110042
      • Novartis Investigative Site
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Novartis Investigative Site
• Czechia
  • Brno, Czechia, 65653
    • Novartis Investigative Site
  • CZE
    • Olomouc, CZE, Czechia, 775 20
      • Novartis Investigative Site
  • Czech Republic
    • Brno Bohunice, Czech Republic, Czechia, 625 00
      • Novartis Investigative Site
• France
  • Angers Cedex 02, France, 49055
    • Novartis Investigative Site
  • Avignon Cedex, France, 84082
    • Novartis Investigative Site
  • Besancon cedex, France, 25030
    • Novartis Investigative Site
  • Bordeaux, France, 33076
    • Novartis Investigative Site
  • Caen Cedex, France, 14021
    • Novartis Investigative Site
  • Clermont-Ferrand, France, 63011
    • Novartis Investigative Site
  • Le Mans Cedex, France, 72015
    • Novartis Investigative Site
  • Lille Cedex, France, 59020
    • Novartis Investigative Site
  • Montpellier Cedex 5, France, 34298
    • Novartis Investigative Site
  • Paris, France, 75231
    • Novartis Investigative Site
  • Paris, France, 75010
    • Novartis Investigative Site
  • Rouen Cedex 1, France, 76038
    • Novartis Investigative Site
  • Saint-Herblain Cédex, France, 44805
    • Novartis Investigative Site
  • Strasbourg cedex, France, 67085
    • Novartis Investigative Site
  • Toulouse Cedex 9, France, 31059
    • Novartis Investigative Site
  • Villejuif Cedex, France, 94800
    • Novartis Investigative Site
  • Alpes Maritimes
    • Nice Cedex 2, Alpes Maritimes, France, 06189
      • Novartis Investigative Site
  • Cote D Or
    • Dijon Cedex, Cote D Or, France, 21034
      • Novartis Investigative Site
  • Loire
    • Saint Priest en Jarez, Loire, France, 42270
      • Novartis Investigative Site
• Germany
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Hamburg, Germany, 20249
    • Novartis Investigative Site
  • Hannover, Germany, 30177
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
  • Kiel, Germany, 24105
    • Novartis Investigative Site
  • Magdeburg, Germany, 39108
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Mannheim, Germany, 68165
    • Novartis Investigative Site
  • Mühlhausen, Germany, 99974
    • Novartis Investigative Site
  • München, Germany, 80638
    • Novartis Investigative Site
  • Saarbruecken, Germany, 66113
    • Novartis Investigative Site
  • Velbert, Germany, 42551
    • Novartis Investigative Site
  • Wuerzburg, Germany, 97080
    • Novartis Investigative Site
  • Hessen
    • Langen, Hessen, Germany, 63225
      • Novartis Investigative Site
  • North Rhine-westphalia
    • Recklinghausen, North Rhine-westphalia, Germany, 45657
      • Novartis Investigative Site
  • Schleswig-holstein
    • Luebeck, Schleswig-holstein, Germany, 23563
      • Novartis Investigative Site
• Greece
  • Athens, Greece, 115 28
    • Novartis Investigative Site
  • Heraklion Crete, Greece, 711 10
    • Novartis Investigative Site
  • Patras, Greece, 265 00
    • Novartis Investigative Site
  • GR
    • Thessaloniki, GR, Greece, 54645
      • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, H 1122
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
  • Miskolc, Hungary, 3526
    • Novartis Investigative Site
  • Szolnok, Hungary, H-5000
    • Novartis Investigative Site
• Israel
  • Haifa, Israel, 3525408
    • Novartis Investigative Site
  • Jerusalem, Israel, 91120
    • Novartis Investigative Site
  • Petach Tikva, Israel, 49100
    • Novartis Investigative Site
  • Ramat Gan, Israel, 52621
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • Bologna, Italy, 40138
    • Novartis Investigative Site
  • Napoli, Italy, 80131
    • Novartis Investigative Site
  • CN
    • Cuneo, CN, Italy, 12100
      • Novartis Investigative Site
  • CR
    • Cremona, CR, Italy, 26100
      • Novartis Investigative Site
  • CZ
    • Catanzaro, CZ, Italy, 88100
      • Novartis Investigative Site
  • FC
    • Meldola, FC, Italy, 47014
      • Novartis Investigative Site
  • FI
    • Firenze, FI, Italy, 50134
      • Novartis Investigative Site
  • LU
    • Lido di Camaiore, LU, Italy, 55041
      • Novartis Investigative Site
  • MC
    • Macerata, MC, Italy, 62100
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20162
      • Novartis Investigative Site
    • Milano, MI, Italy, 20133
      • Novartis Investigative Site
    • Milano, MI, Italy, 20141
      • Novartis Investigative Site
    • Milano, MI, Italy, 20122
      • Novartis Investigative Site
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
  • PI
    • Pisa, PI, Italy, 56126
      • Novartis Investigative Site
  • PN
    • Aviano, PN, Italy, 33081
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00128
      • Novartis Investigative Site
    • Roma, RM, Italy, 00161
      • Novartis Investigative Site
    • Roma, RM, Italy, 00189
      • Novartis Investigative Site
  • RN
    • Rimini, RN, Italy, 47900
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10126
      • Novartis Investigative Site
  • VE
    • Mirano, VE, Italy, 30035
      • Novartis Investigative Site
• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 464 8681
      • Novartis Investigative Site
  • Chiba
    • Kashiwa, Chiba, Japan, 277 8577
      • Novartis Investigative Site
  • Fukuoka
    • Fukuoka-city, Fukuoka, Japan, 811-1395
      • Novartis Investigative Site
  • Gunma
    • Maebashi city, Gunma, Japan, 371 8511
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo-city, Hokkaido, Japan, 003-0804
      • Novartis Investigative Site
  • Kanagawa
    • Isehara, Kanagawa, Japan, 259-1193
      • Novartis Investigative Site
    • Yokohama-city, Kanagawa, Japan, 241-8515
      • Novartis Investigative Site
  • Kumamoto
    • Kumamoto City, Kumamoto, Japan, 860-8556
      • Novartis Investigative Site
  • Kyoto
    • Sakyo Ku, Kyoto, Japan, 606 8507
      • Novartis Investigative Site
  • Osaka
    • Osaka-city, Osaka, Japan, 540-0006
      • Novartis Investigative Site
    • Osaka-city, Osaka, Japan, 541-8567
      • Novartis Investigative Site
    • Suita city, Osaka, Japan, 565 0871
      • Novartis Investigative Site
  • Tokyo
    • Koto ku, Tokyo, Japan, 135 8550
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 06351
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 03722
    • Novartis Investigative Site
  • Gyeonggi-do
    • Suwon, Gyeonggi-do, Korea, Republic of, 443380
      • Novartis Investigative Site
  • Seocho Gu
    • Seoul, Seocho Gu, Korea, Republic of, 06591
      • Novartis Investigative Site
• Netherlands
  • Nijmegen, Netherlands, 6500 HB
    • Novartis Investigative Site
• Peru
  • Lima
    • Surquillo, Lima, Peru, 34
      • Novartis Investigative Site
• Poland
  • Kraków, Poland
    • Novartis Investigative Site
  • Olsztyn, Poland, 10-513
    • Novartis Investigative Site
  • Warszawa, Poland, 02-776
    • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Novartis Investigative Site
  • Moscow, Russian Federation, 115998
    • Novartis Investigative Site
  • Nizhniy Novgorod, Russian Federation, 603081
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 197758
    • Novartis Investigative Site
  • St- Petersburg, Russian Federation, 197022
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 169610
    • Novartis Investigative Site
• Slovakia
  • Kosice, Slovakia, 041 91
    • Novartis Investigative Site
  • Slovak Republic
    • Bratislava, Slovak Republic, Slovakia, 83310
      • Novartis Investigative Site
• South Africa
  • Johannesburg, South Africa, 2196
    • Novartis Investigative Site
  • Parktown, South Africa, 2193
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28033
    • Novartis Investigative Site
  • Madrid, Spain, 28050
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Madrid, Spain, 28222
    • Novartis Investigative Site
  • Zaragoza, Spain, 50009
    • Novartis Investigative Site
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Novartis Investigative Site
  • Andalucia
    • Cordoba, Andalucia, Spain, 14004
      • Novartis Investigative Site
    • Jaen, Andalucia, Spain, 23007
      • Novartis Investigative Site
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41013
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41009
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41014
      • Novartis Investigative Site
  • Asturias
    • Oviedo, Asturias, Spain, 33006
      • Novartis Investigative Site
  • Castilla La Mancha
    • Toledo, Castilla La Mancha, Spain, 45071
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08003
      • Novartis Investigative Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08024
      • Novartis Investigative Site
    • Tarragona, Cataluña, Spain, 43007
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46026
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46009
      • Novartis Investigative Site
  • Las Palmas De Gran Canaria
    • Las Palmas De Gran Canarias, Las Palmas De Gran Canaria, Spain, 35016
      • Novartis Investigative Site
  • Madrid
    • San Sebastian de los Reyes, Madrid, Spain, 28702
      • Novartis Investigative Site
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Novartis Investigative Site
• Switzerland
  • Bellinzona, Switzerland, 6500
    • Novartis Investigative Site
  • Genève, Switzerland, 1211
    • Novartis Investigative Site
  • Zuerich, Switzerland, 8038
    • Novartis Investigative Site
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Novartis Investigative Site
  • Kaohsiung, Taiwan, 833
    • Novartis Investigative Site
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Taipei, Taiwan, 10048
    • Novartis Investigative Site
  • Taipei, Taiwan, 112
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10330
    • Novartis Investigative Site
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • Novartis Investigative Site
  • Derby, United Kingdom, DE22 3NE
    • Novartis Investigative Site
  • Leicester, United Kingdom, LE1 5WW
    • Novartis Investigative Site
  • Liverpool, United Kingdom, L7 8XP
    • Novartis Investigative Site
  • London, United Kingdom, SE1 9RT
    • Novartis Investigative Site
  • London, United Kingdom, WC1E 6HX
    • Novartis Investigative Site
  • Manchester, United Kingdom, M20 2BX
    • Novartis Investigative Site
  • Oxford, United Kingdom, OX3 7LJ
    • Novartis Investigative Site
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Novartis Investigative Site
• United States
  • Alabama
    • Mobile, Alabama, United States, 36688
      • University of South Alabama / Mitchell Cancer Institute Deptof Mitchell Cancer Inst(2)
  • Arizona
    • Phoenix, Arizona, United States
      • Arizona Oncology Associates Dept of Oncology
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • California
    • Arcadia, California, United States, 91007
      • Shapiro and Stafford and Yee and Polanski Study Coordinator
    • Fresno, California, United States, 93720
      • Cancer Care Associates Dept.ofCancerCareAssoc.
    • Fullerton, California, United States, 92835
      • St. Jude Heritage Medical Group Virginia Crosson Cancer Center
    • La Jolla, California, United States, 92093-0658
      • University of California San Diego - Moores Cancer Center UCSD 3
    • Los Angeles, California, United States, 90017
      • Los Angeles Hematology/Oncology Medical Group LA Cancer Network
    • Los Angeles, California, United States, 90053
      • USC Kenneth Norris Comprehensive Cancer Center Dept.ofNorrisCompCancerCtr (3)
    • Los Angeles, California, United States, 90095
      • University of California at Los Angeles Dept. of UCLA
    • Oxnard, California, United States, 93030
      • Ventura County Hematology and Oncology PMK Medical Group
    • San Luis Obispo, California, United States, 93401
      • Coastal Integrative Cancer Care
    • Santa Barbara, California, United States, 93105
      • Santa Barbara Hematolgy Oncology Medical Group
    • Santa Maria, California, United States, 93454
      • Central Coast Medical Oncology Corporation
    • Santa Rosa, California, United States, 94503
      • St Joseph Heritage Healthcare Dept. of RRMG (4)
    • Valencia, California, United States, 91355
      • Granada Hills Cancer Center
  • Colorado
    • Denver, Colorado, United States
      • Kaiser Permanente Northwest Kaiser
    • Greenwood Village, Colorado, United States
      • Rocky Mountain Cancer Centers RMCC
  • Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Cancer Center MRCC
    • Jacksonville, Florida, United States, 32258
      • Cancer Specialists of North Florida SC - F2302
    • Miami, Florida, United States, 33136
      • University Of Miami Univ Miami 2
    • Orlando, Florida, United States, 32806
      • MD Anderson Cancer Center - Orlando MD Orlando
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Georgia Cancer Specialists SC
  • Illinois
    • Evanston, Illinois, United States, 60201
      • North Shore University Health System
    • Geneva, Illinois, United States, 60134
      • Cadence Health
    • Multiple Locations, Illinois, United States
      • Cancer Care and Hematology Specialists of Chicagoland Niles
  • Kansas
    • Wichita, Kansas, United States, 67214-3728
      • Cancer Center of Kansas CCK
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center Mercy Medical SC
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Med Sidney/John Hopkins
    • Frederick, Maryland, United States, 21701
      • Frederick Memorial Hospital Fred. Mem. Hosp.
    • Rockville, Maryland, United States, 20850
      • Maryland Oncology Hematology, P.A. SC
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital SC
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center Dept of Oncology
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Hematology and Oncology Association at Bridgepoint Hem Onc Bridgepoint
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine Regulatory
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • Hackensack Meridian Health
    • Paramus, New Jersey, United States, 07652
      • The Valley Hospital / Luckow Pavillion
  • New York
    • Lake Success, New York, United States, 11042
      • Clinical Research Alliance SC-2
    • New York, New York, United States, 10017
      • Memorial Sloan Kettering Dept Onc
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center Univ Rochester
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Levine Cancer Institute Levine Cancer Institute
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cleveland, Ohio, United States, 44106-5000
      • Case Western Reserve SC
  • Oregon
    • Portland, Oregon, United States, 97210
      • Northwest Cancer Specialists Portland Loc
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's Hospital and Health Network St Luke's (2)
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Charleston Hematology Oncology Association PA
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Tennessee Cancer Specialists
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center Vanderbilt - Thompson Ln
  • Texas
    • Dallas, Texas, United States, 75251
      • Texas Oncology P A TX Onc - Med City Dallas
    • Dallas, Texas, United States, 75251
      • Texas Oncology P A Midtown
    • Dallas, Texas, United States, 75251
      • Texas Oncology P A TX Onc - Bedford
    • Dallas, Texas, United States, 75251
      • Texas Oncology P A TX Onc - Southwest
    • Houston, Texas, United States, 77024
      • Oncology Consultants Oncology Consultants, P.A.
    • San Antonio, Texas, United States, 78229
      • Cancer Therapy and Research Center UT Health Science Center Institute for Drug Development
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Oncology Hematology Associates of Southeast Virginia Salem VA Branch
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology Kadlec Clinic Hematology & Onc
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University/ Mary Babb Randolph Cancer Center Dept of Oncology
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54313
      • Cancer TEAM Bellin Health Belin Health
    • Madison, Wisconsin, United States, 53792-6164
      • University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc 3
    • Madison, Wisconsin, United States, 53717
      • Dean Health System Dean Hematology Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Key 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

Key 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BKM120 100mg + Fulvestrant; BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	Drug: Fulvestrant; Intramuscular fulvestrant 500 mg (Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter); Drug: BKM120; BKM120 100 mg once daily
Placebo Comparator: Placebo + Fulvestrant; BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.	Drug: Fulvestrant; Intramuscular fulvestrant 500 mg (Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter); Drug: BKM120 matching placebo; BKM120 matching placebo, once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort	Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not progress or die at the time of the analysis data cut-off or start of new antineoplastic therapy, PFS was censored at the date of the last adequate tumor assessment before the earliest of the cut-off date or the start date of additional anti-neoplastic therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria RECIST v1.1, as 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline and/or unequivocal progression of the non-target lesions and/or appearance of a new lesion. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm.	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 up to approximately 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort	Overall Survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive. Patients were followed up for the duration of the study and for an expected average of every 3 months after end of treatment.	Every 3 months following end of treatment visit, assessed for approximately 5 years
Overall Response Rate (ORR) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort	Overall Response Rate (ORR) is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1. ORR was analyzed in the full population. Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for target/non target lesions: Complete Response (CR), disappearance of all target/non target lesions (all lymph nodes assigned as non-target lesions must be non-pathological in size (< 10 mm short axis)); Partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions ; Overall Response (OR)= CR+PR. Only descriptive analysis performed.	From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 5 years
Clinical Benefit Rate (CBR) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort	Clinical Benefit Rate (CBR) is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) or Non-CR/non-PD lasting more than 24 weeks based on local investigator's assessment according to RECIST 1.1. CBR was analyzed in the full population. Only descriptive analysis performed.	From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 5 years
Number of Participants With On-Treatments Adverse Events, Serious Adverse Events and Deaths	Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths. Only descriptive analysis performed.	From first dose of study treatment to 30 days after last dose of study treatment, assessed for approximately 5 years
Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 2 Day 1	Plasma samples were collected from the first 200 BKM120-treated patients on Cycle 2 Day 1 (at pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h and 24h [before Cycle 2 Day 2 dose] post-dose). Each cycle is 28 days. Only descriptive analysis performed.	Cycle2 Day1 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours post-dose). Each cycle is 28 days.
Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS)	Pre-dose samples were collected for trough concentrations at Cycle 2 Day 1, Cycle 2 Day 15 and Cycle 3 Day 1. Each cycle is 28 days. Only descriptive analysis performed.	Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1. Each cycle is 28 days.
Median Time to Definitive Deterioration of the ECOG Performance Status - Full Analysis Set (FAS)	Time to definitive deterioration of the ECOG PS was defined as the time between the date of randomization and the date of the assessment at which definitive deterioration was seen. Only descriptive analysis performed.	Up to approx 27 months
Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30	The global health status/QoL scale score of the QLQ-C30 is identified as the primary PRO variable of interest. Physical Functioning (PF), Emotional Functioning (EF) and Social Functioning (SF) scale scores of the QLQ-C30. The time to definitive 10% deterioration is defined as the time from the randomization date to the date of an event, which is defined as a worsening (decrease) in score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study or death due to any cause. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high /healthy level of functioning, a high score for the global health status / QoL represents a high QoL. Patients were assessed up to approx. 8.3 months. Only descriptive analysis performed.	Cycle 1 day 1, cycle 1 day 15, 6 weeks after randomisation and then every 8 weeks until end of treatment

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.
• 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. Erratum In: Lancet Oncol. 2019 Feb;20(2):e71-e72.

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2012
• Primary Completion (Actual): April 29, 2015
• Study Completion (Actual): April 19, 2019

Study Registration Dates

• First Submitted: May 11, 2012
• First Submitted That Met QC Criteria: June 1, 2012
• First Posted (Estimate): June 4, 2012

Study Record Updates

• Last Update Posted (Actual): August 25, 2020
• Last Update Submitted That Met QC Criteria: August 24, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Breast cancer; Refractory; Metastatic; Hormone receptor positive; Locally advanced; Fulvestrant; PI3K; Aromatase inhibitor; HER2-negative
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant
• Other Study ID Numbers: CBKM120F2302; 2011-005524-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No