A Study of the Experimental Drug BKM120 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Activation

Breast Cancer Clinical Trial

— BELLE-4  

Official title:

A Randomized, Double-blind, Placebo Controlled, Phase II/III Study of BKM120 Plus Paclitaxel in Patients With HER2 Negative Inoperable Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Pathway Activation.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01572727
• Other study ID #: CBKM120F2202
• Secondary ID: 2011-005932-24
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: April 4, 2012
• Last updated: January 11, 2016
• Start date: August 2012
• Est. completion date: June 2015

Study information

• Verified date: January 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustria: Agency for Health and Food SafetyBelgium: Federal Agency for Medicinal Products and Health ProductsCzech Republic: State Institute for Drug ControlSpain: Spanish Agency of MedicinesFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Hungary: National Institute of PharmacyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Hong Kong: Department of HealthBrazil: ENVISAItaly: National Institute of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencySouth Korea: Korea Food and Drug Administration (KFDA)Russia: Ministry of Health of the Russian FederationSingapore: Health Sciences AuthorityTaiwan : Food and Drug AdministrationAustralia: Department of Health and Ageing Therapeutic Goods AdministrationIsrael: Ministry of HealthSouth Africa: Medicine Regulatory Authority (MRA)Canada: Health CanadaGermany: Federal Institute for Drugs and Medical Devices (BfArM)Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

This study will evaluate whether the addition of daily BKM120 to weekly paclitaxel is effective and safe in treating patients with HER2- locally advanced or metastatic breast cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 416
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Breast cancer that is locally advanced or metastatic

• HER2 negative disease, and a known hormone receptor status (common breast cancer classification tests)

• A tumor sample must be shipped to a central lab for identification of biomarkers (PI3K activation status) before randomization

• Adequate bone marrow and organ function

• Measurable or non-measurable disease

Exclusion Criteria:

• Prior chemotherapy for locally advanced or metastatic disease

• Previous treatment with PI3K or AKT inhibitors

• Symptomatic brain metastases

• Concurrent malignancy or malignancy within 3 years prior to start of study treatment

• Certain drugs or radiation within 2-4 weeks of enrollment

• Increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent

• Active heart (cardiac) disease as defined in the protocol

• Known hypersensitivity or contraindications to use paclitaxel

• Pregnant or nursing (lactating) woman

• Certain scores on an anxiety and depression mood questionaire given at screening

• Other protocol defined criteria may apply

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Paclitaxel
intravenous paclitaxel 80 mg/m2 per week.
• BKM120 matching placebo
BKM120 matching placebo, daily oral capsules
• BKM120
BKM120 daily oral capsules

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Geelong	Victoria
Australia	Novartis Investigative Site	Parkville	Victoria
Australia	Novartis Investigative Site	Perth	Western Australia
Australia	Novartis Investigative Site	Sydney	New South Wales
Austria	Novartis Investigative Site	Salzburg
Austria	Novartis Investigative Site	Vienna
Belgium	Novartis Investigative Site	Charleroi
Belgium	Novartis Investigative Site	Liege
Belgium	Novartis Investigative Site	Liège
Belgium	Novartis Investigative Site	Ottignies
Belgium	Novartis Investigative Site	Sint-Niklaas
Belgium	Novartis Investigative Site	Wilrijk
Brazil	Novartis Investigative Site	Fortaleza	CE
Brazil	Novartis Investigative Site	São Paulo	SP
Brazil	Novartis Investigative Site	São Paulo	SP
Brazil	Novartis Investigative Site	São Paulo	SP
Canada	Novartis Investigative Site	Montreal	Quebec
Czech Republic	Novartis Investigative Site	Brno
Czech Republic	Novartis Investigative Site	Olomouc
Czech Republic	Novartis Investigative Site	Praha 2
France	Novartis Investigative Site	Angers Cedex 02
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	La Roche sur Yon cedex 9
France	Novartis Investigative Site	Le Mans Cedex
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Nice Cedex 2
France	Novartis Investigative Site	Saint Herblain cedex
France	Novartis Investigative Site	Toulouse Cedex 9
France	Novartis Investigative Site	Villejuif Cedex
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Fulda
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Ravensburg
Germany	Novartis Investigative Site	Ulm
Hong Kong	Novartis Investigative Site	Hong Kong SAR
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Szolnok
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Tel-Aviv
Italy	Novartis Investigative Site	Cona	FE
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Messina	ME
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Monza	MB
Japan	Novartis Investigative Site	Isehara-city	Kanagawa
Japan	Novartis Investigative Site	Kawasaki-city	Kanagawa
Japan	Novartis Investigative Site	Koto	Tokyo
Japan	Novartis Investigative Site	Kumamoto City	Kumamoto
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Sapporo	Hokkaido
Japan	Novartis Investigative Site	Suita-city	Osaka
Japan	Novartis Investigative Site	Yokohama	Kanagawa
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Netherlands	Novartis Investigative Site	Breda
Netherlands	Novartis Investigative Site	Rotterdam
Russian Federation	Novartis Investigative Site	St. Petersburg
Russian Federation	Novartis Investigative Site	St.- Petersburg	Russia
Singapore	Novartis Investigative Site	Singapore
South Africa	Novartis Investigative Site	Johannesburg
Spain	Novartis Investigative Site	A Coruna	Galicia
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Cordoba	Andalucia
Spain	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya
Spain	Novartis Investigative Site	La Laguna	Santa Cruz de Tenerife
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Zaragoza
Taiwan	Novartis Investigative Site	Kuei-Shan Chiang	Taoyuan/ Taiwan ROC
Taiwan	Novartis Investigative Site	New Taipei City
Taiwan	Novartis Investigative Site	Taipei
United Kingdom	Novartis Investigative Site	Glasgow - Scotland
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Maidstone	Kent
United Kingdom	Novartis Investigative Site	Wirral
United States	University of New Mexico Cancer Research Center Dept of Univ New Mexico	Albuquerque	New Mexico
United States	Emory University School of Medicine/Winship Cancer Institute Dept.of WinshipCancerInst. (2)	Atlanta	Georgia
United States	Ironwood Cancer and Research Centers SC	Chandler	Arizona
United States	Ohio State Comprehensive Cancer Center/James Cancer Hospital SC-1	Columbus	Ohio
United States	Baylor Health Care System/Sammons Cancer Center Baylor Texas Oncology	Dallas	Texas
United States	University of Texas Southwestern Medical Center Harry Hines	Dallas	Texas
United States	Highlands Oncology Group Dept of Highlands Oncology Grp	Fayetteville	Arkansas
United States	California Cancer Care Marian Speciality	Greenbrae	California
United States	Rocky Mountain Cancer Centers RMCC Hale Pkwy	Greenwood Village	Colorado
United States	University of Kansas Cancer Center Univ Kansas 2	Kansas City	Kansas
United States	Norton Healthcare, Inc.	Louisville	Kentucky
United States	Northwest Georgia Oncology Center NW Georgia Onc	Marietta	Georgia
United States	University of Oklahoma Health Sciences Center OUHSC 2	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center Unv Nebraska Med Ctr (2)	Omaha	Nebraska
United States	Arizona Oncology Associates Dept of Oncology	Phoenix	Arizona
United States	Northwest Cancer Specialists Vancouver Loc	Portland	Oregon
United States	Medical Oncology & Hematology Associates of Northern VA Med Onc Hem Northern VA	Reston	Virginia
United States	Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio	San Antonio	Texas
United States	Washington University School of Medicine Regulatory	St. Louis	Missouri
United States	H. Lee Moffitt Cancer Center & Research Institute SC	Tampa	Florida
United States	New York Oncology Hematology, P.C. Dept. of New York Oncology. PC	Troy	New York

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Czech Republic,  France,  Germany,  Hong Kong,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Russian Federation,  Singapore,  South Africa,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression free survival (PFS)	PFS is defined as the time from the date of randomization to the date of the event, defined as the first radiologically documented disease progression or death due to any cause. PFS is based on local investigator assessment	Every 8 weeks after randomization	No
Secondary	overall survival	Time from date of randomization to the date of death from any cause	Every 3 months after end of Treatment	No
Secondary	overall response rate	Proportion of patients with best overall response of complete response (CR) or partial response (PR) based according to RECIST 1.1	Every 8 weeks after randomization	No
Secondary	duration of response	time from the date of the first documented response (CR or PR, which has to be confirmed subsequently) to the date of the first radiologically documented disease progression or death due to disease	Every 8 weeks after randomization	No
Secondary	time to response	time from date of randomization until first documented response (CR or PR, which has to be confirmed subsequently).	Every 8 weeks after randomization	No
Secondary	clinical benefit rate	Proportion of patients with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) lasting more than 24 weeks as defined in RECIST 1.1.	Every 8 weeks after randomization	No
Secondary	Type, frequency and severity of adverse events	Safety will be determine by type, frequency and severity of adverse events per CTCAEv4.03 Type, frequency and severity of laboratory toxicities per CTCAEv4.03	Continuous, until 30 days after treatment stops	Yes
Secondary	Plasma concentration-time profiles of BKM120 - pharmacokinetics (PK)	Summary statistics for PK: plasma concentration-time profiles of BKM120 and appropriate individual PK parameters based on population PK model , if deemed appropriate; each cycle = 28 days	Cycle 1 day 1, 15, 16, 22 and Cycle 2 day 1.	No
Secondary	Time to definitive deterioration of ECOG performance status	Time to definitive deterioration of the ECOG performance status from baseline	every 4 weeks	No