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)

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

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).

Study Overview

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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 432
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1050AAK
      • Novartis Investigative Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000KZE
      • Novartis Investigative Site
  • Tucuman
    • San Miguel De Tucuman, Tucuman, Argentina, T4000IAK
      • Novartis Investigative Site
  • Viedma
    • Rio Negro, Viedma, Argentina, 8500
      • Novartis Investigative Site
• Austria
  • Linz, Austria, 4010
    • Novartis Investigative Site
  • Salzburg, Austria, 5020
    • Novartis Investigative Site
  • Wien, Austria, A-1090
    • Novartis Investigative Site
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1000
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
  • Liege, Belgium, 4000
    • Novartis Investigative Site
  • Namur, Belgium, 5000
    • Novartis Investigative Site
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • Novartis Investigative Site
  • Plovdiv, Bulgaria, 4004
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1527
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1756
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1303
    • Novartis Investigative Site
  • Varna, Bulgaria, 9010
    • Novartis Investigative Site
  • Vratsa, Bulgaria, 3000
    • Novartis Investigative Site
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2W 1T8
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H3A 1A1
      • Novartis Investigative Site
• Colombia
  • Bogota, Colombia
    • Novartis Investigative Site
  • Monteria, Colombia
    • Novartis Investigative Site
• Finland
  • Tampere, Finland, FIN-33521
    • Novartis Investigative Site
• France
  • Angers Cedex 02, France, 49055
    • Novartis Investigative Site
  • Clermont-Ferrand, France, 63011
    • Novartis Investigative Site
  • Lyon Cedex, France, 69373
    • Novartis Investigative Site
  • Paris, France, 75231
    • Novartis Investigative Site
  • Rouen Cedex 1, France, 76038
    • Novartis Investigative Site
  • Saint-Brieuc Cédex, France, 22015
    • Novartis Investigative Site
  • Saint-Herblain Cédex, France, 44805
    • Novartis Investigative Site
  • Alpes Maritimes
    • Nice Cedex 2, Alpes Maritimes, France, 06189
      • Novartis Investigative Site
  • Haute Vienne
    • Limoges cedex, Haute Vienne, France, 87000
      • Novartis Investigative Site
  • Hauts De Seine
    • Saint-Cloud, Hauts De Seine, France, 92210
      • Novartis Investigative Site
  • Marne
    • Reims Cedex, Marne, France, 51056
      • Novartis Investigative Site
• Germany
  • Berlin, Germany, 12203
    • Novartis Investigative Site
  • Bonn, Germany, 53111
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Essen, Germany, 45136
    • Novartis Investigative Site
  • Frankfurt, Germany, 60389
    • Novartis Investigative Site
  • Fulda, Germany, 36043
    • Novartis Investigative Site
  • Karlsruhe, Germany, 76135
    • Novartis Investigative Site
  • Kiel, Germany, 24103
    • Novartis Investigative Site
  • Leer, Germany, 26789
    • Novartis Investigative Site
  • Magdeburg, Germany, 39120
    • Novartis Investigative Site
  • Mannheim, Germany, 68165
    • Novartis Investigative Site
  • Muenchen, Germany, 81377
    • Novartis Investigative Site
  • Muenchen, Germany, 80637
    • Novartis Investigative Site
  • Mühlhausen, Germany, 99974
    • Novartis Investigative Site
  • Ravensburg, Germany, 88214
    • Novartis Investigative Site
  • Soest, Germany, 59494
    • Novartis Investigative Site
  • Tuebingen, Germany, 72076
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • Velbert, Germany, 42551
    • Novartis Investigative Site
  • Nordrhein-Westfalen
    • Koeln, Nordrhein-Westfalen, Germany, 50937
      • Novartis Investigative Site
• Greece
  • Athens, Greece, 18547
    • Novartis Investigative Site
  • Athens, Greece, GR-115 22
    • Novartis Investigative Site
  • Heraklion Crete, Greece, 711 10
    • Novartis Investigative Site
  • Athens
    • Marousi, Athens, Greece, 15123
      • Novartis Investigative Site
  • GR
    • Athens, GR, Greece, 151 23
      • Novartis Investigative Site
    • Larissa, GR, Greece, 411 10
      • Novartis Investigative Site
    • Patra - RIO, GR, Greece, 265 04
      • Novartis Investigative Site
  • Thessaloniki
    • Thesaloniki, Thessaloniki, Greece, 54622
      • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, H-1122
    • Novartis Investigative Site
  • Budapest, Hungary, 1134
    • Novartis Investigative Site
  • Szeged, Hungary, H-6720
    • Novartis Investigative Site
  • Szolnok, Hungary, H-5000
    • Novartis Investigative Site
• Italy
  • Frattamaggiore, Italy, 80020
    • Novartis Investigative Site
  • AQ
    • L'Aquila, AQ, Italy, 67100
      • Novartis Investigative Site
  • BA
    • Bari, BA, Italy, 70124
      • Novartis Investigative Site
  • BN
    • Benevento, BN, Italy, 82100
      • Novartis Investigative Site
  • BR
    • Brindisi, BR, Italy, 72100
      • Novartis Investigative Site
  • BS
    • Brescia, BS, Italy, 25123
      • Novartis Investigative Site
  • CA
    • Monserrato, CA, Italy, 09042
      • Novartis Investigative Site
  • CR
    • Cremona, CR, Italy, 26100
      • Novartis Investigative Site
  • CT
    • Catania, CT, Italy, 95100
      • Novartis Investigative Site
  • FC
    • Meldola, FC, Italy, 47014
      • Novartis Investigative Site
  • FE
    • Cona, FE, Italy, 44100
      • Novartis Investigative Site
  • FI
    • Firenze, FI, Italy, 50134
      • Novartis Investigative Site
  • FR
    • Sora, FR, Italy, 03039
      • Novartis Investigative Site
  • LC
    • Lecco, LC, Italy, 23900
      • Novartis Investigative Site
  • LE
    • Lecce, LE, Italy, 73100
      • Novartis Investigative Site
  • MB
    • Monza, MB, Italy, 20900
      • Novartis Investigative Site
  • MC
    • Macerata, MC, Italy, 62100
      • Novartis Investigative Site
  • ME
    • Messina, ME, Italy, 98158
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20132
      • Novartis Investigative Site
    • Milano, MI, Italy, 20141
      • Novartis Investigative Site
    • Milano, MI, Italy, 20121
      • Novartis Investigative Site
  • MO
    • Modena, MO, Italy, 41124
      • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35100
      • Novartis Investigative Site
  • PI
    • Pisa, PI, Italy, 56126
      • Novartis Investigative Site
  • PN
    • Pordenone, PN, Italy, 33170
      • Novartis Investigative Site
  • PO
    • Prato, PO, Italy, 59100
      • Novartis Investigative Site
  • PR
    • Parma, PR, Italy, 43100
      • Novartis Investigative Site
  • PV
    • Pavia, PV, Italy, 27100
      • Novartis Investigative Site
  • RC
    • Reggio Calabria, RC, Italy, 89124
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00168
      • Novartis Investigative Site
    • Roma, RM, Italy, 00128
      • Novartis Investigative Site
  • SA
    • Salerno, SA, Italy, 84131
      • Novartis Investigative Site
  • SS
    • Sassari, SS, Italy, 07100
      • Novartis Investigative Site
  • TO
    • Candiolo, TO, Italy, 10060
      • Novartis Investigative Site
    • Ivrea, TO, Italy, 10015
      • Novartis Investigative Site
    • Torino, TO, Italy, 10126
      • Novartis Investigative Site
  • VE
    • Mirano, VE, Italy, 30035
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37126
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Novartis Investigative Site
  • Korea
    • Gyeonggi-do, Korea, Korea, Republic of, 10408
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 05505
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 03080
      • Novartis Investigative Site
• Lebanon
  • Ashrafieh, Lebanon, 166830
    • Novartis Investigative Site
  • Beirut, Lebanon
    • Novartis Investigative Site
  • Saida, Lebanon, 652
    • Novartis Investigative Site
• Netherlands
  • Breda, Netherlands, 4819 EV
    • Novartis Investigative Site
  • Delft, Netherlands, NL 2625 AD
    • Novartis Investigative Site
  • Deventer, Netherlands, 7416 SE
    • Novartis Investigative Site
  • Hoofddorp, Netherlands, 2134 TM
    • Novartis Investigative Site
  • Leiden, Netherlands, 2300 RC
    • Novartis Investigative Site
  • Sittard-Geleen, Netherlands, 6162 BG
    • Novartis Investigative Site
  • Zwolle, Netherlands, 8025 AB
    • Novartis Investigative Site
  • AZ
    • Maastricht, AZ, Netherlands, 5800
      • Novartis Investigative Site
• Norway
  • Bergen, Norway, 5021
    • Novartis Investigative Site
  • Oslo, Norway, NO 0450
    • Novartis Investigative Site
• Poland
  • Olsztyn, Poland, 10226
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28007
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Madrid, Spain, 28222
    • Novartis Investigative Site
  • Santa Cruz de Tenerife, Spain, 38009
    • Novartis Investigative Site
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Novartis Investigative Site
  • Andalucia
    • Jaen, Andalucia, Spain, 23007
      • Novartis Investigative Site
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41009
      • Novartis Investigative Site
  • Catalunya
    • Badalona, Catalunya, Spain, 08916
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08003
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Castellon, Comunidad Valenciana, Spain, 12002
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46014
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46009
      • Novartis Investigative Site
  • Galicia
    • La Coruna, Galicia, Spain, 15006
      • Novartis Investigative Site
    • Santiago de Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
  • Islas Baleares
    • Palma De Mallorca, Islas Baleares, Spain, 07120
      • Novartis Investigative Site
  • Santa Cruz De Tenerife
    • La Laguna, Santa Cruz De Tenerife, Spain, 38320
      • Novartis Investigative Site
• Sweden
  • Kalmar, Sweden, SE-391 85
    • Novartis Investigative Site
  • Stockholm, Sweden, SE-171 76
    • Novartis Investigative Site
  • Uppsala, Sweden, 751 85
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Novartis Investigative Site
  • London, United Kingdom, SW3 6JJ
    • Novartis Investigative Site
  • London, United Kingdom, SM2 5PT
    • Novartis Investigative Site
  • Manchester, United Kingdom, M20 2BX
    • Novartis Investigative Site
  • Nottingham, United Kingdom, NG5 1PB
    • Novartis Investigative Site
  • Lancashire
    • Blackburn, Lancashire, United Kingdom, BB2 3HH
      • Novartis Investigative Site
  • Suffolk
    • Ipswich, Suffolk, United Kingdom, IP4 5PD
      • Novartis Investigative Site
• United States
  • Alabama
    • Mobile, Alabama, United States, 36688
      • University of South Alabama / Mitchell Cancer Institute Univ South AL
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer and Research Centers SC
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • California
    • Fountain Valley, California, United States, 92708
      • Compassionate Cancer Care Medical Group CCCMG
    • Los Angeles, California, United States, 90095
      • University of California at Los Angeles UCLA SC
    • Los Angeles, California, United States, 90017
      • Los Angeles Hematology/Oncology Medical Group Onc Dept.
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center SC-5
    • Monterey, California, United States, 93940
      • Pacific Cancer Care
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers SC
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center, LLC
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine/Winship Cancer Institute Emory
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Moanalua Medical Center. Attn: Oncology Dept
  • Illinois
    • Naperville, Illinois, United States, 60540
      • Edward Hospital Edward Hospital
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Crescent City Research Consortium, LLC SC
    • New Orleans, Louisiana, United States, 70115
      • Lsu Health Sciences Center/ Lsu School of Medicine Lsu
    • New Orleans, Louisiana, United States, 70121
      • John Ochsner Heart and Vascular Institute Clinical Trials Ochsner 2
    • New Orleans, Louisiana, United States, 70122-2822
      • LSU Health Sciences Center Feist-Weiller Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center Univ Maryland
  • Missouri
    • Manchester, Missouri, United States, 63021
      • Mercy Medical Research Institute SC
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Morristown Memorial Hospital Morristown Mem
    • Voorhees, New Jersey, United States, 08043
      • CINJ at Cooper University Hospital Dept of Onc
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center Montefiore
    • Lake Success, New York, United States, 11042
      • Clinical Research Alliance
    • Lake Success, New York, United States, 11042
      • Clinical Research Alliance BKM120F2303
  • Oregon
    • Portland, Oregon, United States, 97210
      • Northwest Cancer Specialists Compass Oncology -BKM
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University SC-5
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute Dept of Magee Women's Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • The West Clinic Dept. of the West Clinic
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75246
      • Texas Oncology Texas Oncology - Sammons
    • Dallas, Texas, United States, 75231
      • Texas Oncology PA Dallas Presbyterian Hospital SC
    • Dallas, Texas, United States, 75251
      • Texas Oncology P A SC-Austin
    • Dallas, Texas, United States, 75251
      • Texas Oncology P A Texas Oncology - Fort Worth (3
    • El Paso, Texas, United States, 79905
      • Texas Tech University Health Science Center Dept of Texas Tech
    • Houston, Texas, United States, 77030
      • The Methodist Hospital Cancer Center
    • Tyler, Texas, United States, 75702
      • US Oncology, P.A.
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Key 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

Key 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

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)	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. Patients were followed up for approximately every 6 weeks after randomization.	Every 6 weeks after randomization up to a maximum of 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) - Full Analysis Set (FAS)	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 approximately every 6 weeks after randomization and every 3 months during survival follow-up.	Every 6 weeks after randomization up to a maximum of 5 years
Progression Free Survival (PFS) by PIK3CA Mutational Status	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. Patients were followed up for approximately every 6 weeks after randomization.	Every 6 weeks after randomization up to a maximum of 5 years
Overall Survival (OS) by PIK3CA Mutational Status	Overall Survival (OS) by PIK3CA mutational status based on ctDNA 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 approximately every 6 weeks after randomization and every 3 months during survival follow-up.	Every 6 weeks after randomization up to a maximum of 5 years
Overall Response Rate (ORR) by PIK3CA Mutational Status	Overall Response Rate (ORR) is defined as the proportion 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 and by PIK3CA mutational status based on ctDNA. 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. Patients were followed up for the duration of the study and for approximately every 6 weeks after randomization.	Every 6 weeks after randomization up to a maximum of 5 years
Clinical Benefit Rate (CBR) by PIK3CA Mutational Status	Clinical Benefit Rate (CBR) is defined as the proportion 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 14 or 24 weeks based on local investigator's assessment according to RECIST 1.1. CBR was analyzed in the full population and by PIK3CA mutational status based on ctDNA. Patients were followed up for the duration of the study and approximately every 6 weeks after randomization.	Week 14, Week 24
Long-term Safety and Tolerability in the Two Treatment Arms - Safety Set (SS)	Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths.	From first dose of study treatment to 30 days after last dose of study treatment, up to 5 years
Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 1 Day 1 - Pharmacokinetic Analysis Set (PAS)	Plasma samples were collected from the first 100 BKM120-treated patients on Cycle 1 Day 1 (at 1h, 2h, and 6h post-dose and a recommended 9h post-dose sample).	C1D1 1 hour post dose, C1D1 2 hour post dose, C1D1 6 hour post dose and C1D1 9 hour post dose
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 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1 and Cycle 4 Day 1.	C1D15, C2D1, C3D1 and C4D1
Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30 - Full Analysis Set (FAS)	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.	Baseline, Week 6 (C2D15), Week 12 (C4D1), then every 8 weeks until discontinuation (a cycle [C] = 4 weeks) up to 5 years.
Time to Definitive Deterioration of ECOG Performance Status From Baseline - Full Analysis Set (FAS)	The Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale used to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. The ECOG Performance Scores has 5 grades: 0 = fully active, able to carry on all pre-disease performance without restriction, 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work, 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours, 3 = capable of only limited self-care, confined to bed or chair more than 50% of waking hours, 4 = completely disabled, cannot carry on any self-care, totally confined to bed or chair and 5 = dead. Definitive deterioration is defined as no improvement in the ECOG status following observation of the deterioration.	Screening, Baseline (Cycle 1 Day 1) and then at day 1 of each cycle and at the EOT visit

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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. Erratum In: Lancet Oncol. 2018 Mar;19(3):e137.

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2012
• Primary Completion (Actual): May 23, 2016
• Study Completion (Actual): September 21, 2017

Study Registration Dates

• First Submitted: June 29, 2012
• First Submitted That Met QC Criteria: June 29, 2012
• First Posted (Estimate): July 4, 2012

Study Record Updates

• Last Update Posted (Actual): January 30, 2019
• Last Update Submitted That Met QC Criteria: January 9, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: breast cancer; metastatic; PIK3CA; HR+; HER2-; PI3K; mTOR inhibitor; locally advanced; BKM120; PTEN; fulvestrant; AI treated
• 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: CBKM120F2303; 2012-002571-34 (EudraCT Number)

Plan for Individual participant data (IPD)

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

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