Clinical trial NCT01633060: 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
Official title: A Phase III Randomized, Double Blind, Placebo Controlled Study of BKM120 With Fulvestrant, in Postmenopausal Women With Hormone Receptor-positive HER2-negative AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTOR Inhibitor Based Treatment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Metastatic Breast Cancer
Keywords: BKM120
fulvestrant
breast cancer
metastatic
locally advanced
AI treated
mTOR inhibitor
PI3K
PIK3CA
PTEN
HER2-
HR+
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-07-04
Enrollment: 432
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS)
timeFrame: Every 6 weeks after randomization up to a maximum of 4 years
Secondary outcomes:
measure: Overall Survival (OS) - Full Analysis Set (FAS)
timeFrame: Every 6 weeks after randomization up to a maximum of 5 years
measure: Progression Free Survival (PFS) by PIK3CA Mutational Status
timeFrame: Every 6 weeks after randomization up to a maximum of 5 years
measure: Overall Survival (OS) by PIK3CA Mutational Status
timeFrame: Every 6 weeks after randomization up to a maximum of 5 years
measure: Overall Response Rate (ORR) by PIK3CA Mutational Status
timeFrame: Every 6 weeks after randomization up to a maximum of 5 years
measure: Clinical Benefit Rate (CBR) by PIK3CA Mutational Status
timeFrame: Week 14, Week 24
measure: Long-term Safety and Tolerability in the Two Treatment Arms - Safety Set (SS)
timeFrame: From first dose of study treatment to 30 days after last dose of study treatment, up to 5 years
measure: Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 1 Day 1 - Pharmacokinetic Analysis Set (PAS)
timeFrame: C1D1 1 hour post dose, C1D1 2 hour post dose, C1D1 6 hour post dose and C1D1 9 hour post dose
measure: Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS)
timeFrame: C1D15, C2D1, C3D1 and C4D1
measure: 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)
timeFrame: Baseline, Week 6 (C2D15), Week 12 (C4D1), then every 8 weeks until discontinuation (a cycle [C] = 4 weeks) up to 5 years.
measure: Time to Definitive Deterioration of ECOG Performance Status From Baseline - Full Analysis Set (FAS)
timeFrame: Screening, Baseline (Cycle 1 Day 1) and then at day 1 of each cycle and at the EOT visit
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama / Mitchell Cancer Institute Univ South AL
state: Alabama
city: Chandler
country: United States
facility: Ironwood Cancer and Research Centers SC
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Fountain Valley
country: United States
facility: Compassionate Cancer Care Medical Group CCCMG
state: California
city: Los Angeles
country: United States
facility: Los Angeles Hematology/Oncology Medical Group Onc Dept.
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center SC-5
state: California
city: Los Angeles
country: United States
facility: University of California at Los Angeles UCLA SC
state: California
city: Monterey
country: United States
facility: Pacific Cancer Care
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers SC
state: Colorado
city: Athens
country: United States
facility: University Cancer & Blood Center, LLC
state: Georgia
city: Atlanta
country: United States
facility: Emory University School of Medicine/Winship Cancer Institute Emory
state: Georgia
city: Honolulu
country: United States
facility: Moanalua Medical Center. Attn: Oncology Dept
state: Hawaii
city: Naperville
country: United States
facility: Edward Hospital Edward Hospital
state: Illinois
city: Metairie
country: United States
facility: Crescent City Research Consortium, LLC SC
state: Louisiana
city: New Orleans
country: United States
facility: Lsu Health Sciences Center/ Lsu School of Medicine Lsu
state: Louisiana
city: New Orleans
country: United States
facility: John Ochsner Heart and Vascular Institute Clinical Trials Ochsner 2
state: Louisiana
city: New Orleans
country: United States
facility: LSU Health Sciences Center Feist-Weiller Cancer Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center Univ Maryland
state: Maryland
city: Manchester
country: United States
facility: Mercy Medical Research Institute SC
state: Missouri
city: Morristown
country: United States
facility: Morristown Memorial Hospital Morristown Mem
state: New Jersey
city: Voorhees
country: United States
facility: CINJ at Cooper University Hospital Dept of Onc
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center Montefiore
state: New York
city: Lake Success
country: United States
facility: Clinical Research Alliance BKM120F2303
state: New York
city: Lake Success
country: United States
facility: Clinical Research Alliance
state: New York
city: Portland
country: United States
facility: Northwest Cancer Specialists Compass Oncology -BKM
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University SC-5
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute Dept of Magee Women's Hospital
state: Pennsylvania
city: Memphis
country: United States
facility: The West Clinic Dept. of the West Clinic
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology PA Dallas Presbyterian Hospital SC
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Texas Oncology - Sammons
state: Texas
city: Dallas
country: United States
facility: Texas Oncology P A SC-Austin
state: Texas
city: Dallas
country: United States
facility: Texas Oncology P A Texas Oncology - Fort Worth (3
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: El Paso
country: United States
facility: Texas Tech University Health Science Center Dept of Texas Tech
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital Cancer Center
state: Texas
city: Tyler
country: United States
facility: US Oncology, P.A.
state: Texas
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: San Miguel De Tucuman
country: Argentina
facility: Novartis Investigative Site
state: Tucuman
city: Rio Negro
country: Argentina
facility: Novartis Investigative Site
state: Viedma
city: Innsbruck
country: Austria
facility: Novartis Investigative Site
state: Tyrol
city: Linz
country: Austria
facility: Novartis Investigative Site
city: Salzburg
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Liege
country: Belgium
facility: Novartis Investigative Site
city: Namur
country: Belgium
facility: Novartis Investigative Site
city: Plovdiv
country: Bulgaria
facility: Novartis Investigative Site
city: Plovdiv
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Varna
country: Bulgaria
facility: Novartis Investigative Site
city: Vratsa
country: Bulgaria
facility: Novartis Investigative Site
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Monteria
country: Colombia
facility: Novartis Investigative Site
city: Tampere
country: Finland
facility: Novartis Investigative Site
city: Nice Cedex 2
country: France
facility: Novartis Investigative Site
state: Alpes Maritimes
city: Limoges cedex
country: France
facility: Novartis Investigative Site
state: Haute Vienne
city: Saint-Cloud
country: France
facility: Novartis Investigative Site
state: Hauts De Seine
city: Reims Cedex
country: France
facility: Novartis Investigative Site
state: Marne
city: Angers Cedex 02
country: France
facility: Novartis Investigative Site
city: Clermont-Ferrand
country: France
facility: Novartis Investigative Site
city: Lyon Cedex
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Rouen Cedex 1
country: France
facility: Novartis Investigative Site
city: Saint-Brieuc Cédex
country: France
facility: Novartis Investigative Site
city: Saint-Herblain Cédex
country: France
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Fulda
country: Germany
facility: Novartis Investigative Site
city: Karlsruhe
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Leer
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Mühlhausen
country: Germany
facility: Novartis Investigative Site
city: Ravensburg
country: Germany
facility: Novartis Investigative Site
city: Soest
country: Germany
facility: Novartis Investigative Site
city: Tuebingen
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Velbert
country: Germany
facility: Novartis Investigative Site
city: Marousi
country: Greece
facility: Novartis Investigative Site
state: Athens
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Larissa
country: Greece
facility: Novartis Investigative Site
state: GR
city: Patra - RIO
country: Greece
facility: Novartis Investigative Site
state: GR
city: Thesaloniki
country: Greece
facility: Novartis Investigative Site
state: Thessaloniki
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Heraklion Crete
country: Greece
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Szolnok
country: Hungary
facility: Novartis Investigative Site
city: L'Aquila
country: Italy
facility: Novartis Investigative Site
state: AQ
city: Bari
country: Italy
facility: Novartis Investigative Site
state: BA
city: Benevento
country: Italy
facility: Novartis Investigative Site
state: BN
city: Brindisi
country: Italy
facility: Novartis Investigative Site
state: BR
city: Brescia
country: Italy
facility: Novartis Investigative Site
state: BS
city: Monserrato
country: Italy
facility: Novartis Investigative Site
state: CA
city: Cremona
country: Italy
facility: Novartis Investigative Site
state: CR
city: Catania
country: Italy
facility: Novartis Investigative Site
state: CT
city: Meldola
country: Italy
facility: Novartis Investigative Site
state: FC
city: Cona
country: Italy
facility: Novartis Investigative Site
state: FE
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Sora
country: Italy
facility: Novartis Investigative Site
state: FR
city: Lecco
country: Italy
facility: Novartis Investigative Site
state: LC
city: Lecce
country: Italy
facility: Novartis Investigative Site
state: LE
city: Monza
country: Italy
facility: Novartis Investigative Site
state: MB
city: Macerata
country: Italy
facility: Novartis Investigative Site
state: MC
city: Messina
country: Italy
facility: Novartis Investigative Site
state: ME
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Modena
country: Italy
facility: Novartis Investigative Site
state: MO
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Pordenone
country: Italy
facility: Novartis Investigative Site
state: PN
city: Prato
country: Italy
facility: Novartis Investigative Site
state: PO
city: Parma
country: Italy
facility: Novartis Investigative Site
state: PR
city: Pavia
country: Italy
facility: Novartis Investigative Site
state: PV
city: Reggio Calabria
country: Italy
facility: Novartis Investigative Site
state: RC
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Salerno
country: Italy
facility: Novartis Investigative Site
state: SA
city: Sassari
country: Italy
facility: Novartis Investigative Site
state: SS
city: Candiolo
country: Italy
facility: Novartis Investigative Site
state: TO
city: Ivrea
country: Italy
facility: Novartis Investigative Site
state: TO
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Mirano
country: Italy
facility: Novartis Investigative Site
state: VE
city: Verona
country: Italy
facility: Novartis Investigative Site
state: VR
city: Frattamaggiore
country: Italy
facility: Novartis Investigative Site
city: Gyeonggi-do
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Ashrafieh
country: Lebanon
facility: Novartis Investigative Site
city: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Saida
country: Lebanon
facility: Novartis Investigative Site
city: Maastricht
country: Netherlands
facility: Novartis Investigative Site
state: AZ
city: Breda
country: Netherlands
facility: Novartis Investigative Site
city: Delft
country: Netherlands
facility: Novartis Investigative Site
city: Deventer
country: Netherlands
facility: Novartis Investigative Site
city: Hoofddorp
country: Netherlands
facility: Novartis Investigative Site
city: Leiden
country: Netherlands
facility: Novartis Investigative Site
city: Sittard-Geleen
country: Netherlands
facility: Novartis Investigative Site
city: Zwolle
country: Netherlands
facility: Novartis Investigative Site
city: Bergen
country: Norway
facility: Novartis Investigative Site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Olsztyn
country: Poland
facility: Novartis Investigative Site
city: Elche
country: Spain
facility: Novartis Investigative Site
state: Alicante
city: Jaen
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Badalona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Castellon
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Palma De Mallorca
country: Spain
facility: Novartis Investigative Site
state: Islas Baleares
city: La Laguna
country: Spain
facility: Novartis Investigative Site
state: Santa Cruz De Tenerife
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Santa Cruz de Tenerife
country: Spain
facility: Novartis Investigative Site
city: Kalmar
country: Sweden
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Uppsala
country: Sweden
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Blackburn
country: United Kingdom
facility: Novartis Investigative Site
state: Lancashire
city: Ipswich
country: United Kingdom
facility: Novartis Investigative Site
state: Suffolk
city: Edinburgh
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Nottingham
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.