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 (BELLE-4)

January 27, 2017 updated by: Novartis Pharmaceuticals

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.

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Based on the efficacy results at the time of the interim analyses, the DMC recommended stopping the study at Phase II during the interim as it met the protocol pre-specified futility criteria. Consequently, the Phase III portion of the study was not conducted.

Study Type

Interventional

Enrollment (Actual)

416

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia, 2060
        • Novartis Investigative Site
    • Victoria
      • Geelong, Victoria, Australia, 3220
        • Novartis Investigative Site
      • Parkville, Victoria, Australia, 3050
        • Novartis Investigative Site
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Novartis Investigative Site
  • Austria
      • Salzburg, Austria, 5020
        • Novartis Investigative Site
      • Vienna, Austria, A-1090
        • Novartis Investigative Site
  • Belgium
      • Charleroi, Belgium, 6000
        • Novartis Investigative Site
      • Liege, Belgium, 4000
        • Novartis Investigative Site
      • Liège, Belgium, 4000
        • Novartis Investigative Site
      • Ottignies, Belgium, 1340
        • Novartis Investigative Site
      • Sint-Niklaas, Belgium, 9100
        • Novartis Investigative Site
      • Wilrijk, Belgium, 2610
        • Novartis Investigative Site
  • Brazil
    • CE
      • Fortaleza, CE, Brazil, 60336-045
        • Novartis Investigative Site
    • SP
      • São Paulo, SP, Brazil, 01246-000
        • Novartis Investigative Site
      • São Paulo, SP, Brazil, 01221-020
        • Novartis Investigative Site
      • São Paulo, SP, Brazil, 01317-002
        • Novartis Investigative Site
  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • Novartis Investigative Site
  • Czech Republic
      • Brno, Czech Republic, 656 53
        • Novartis Investigative Site
      • Olomouc, Czech Republic, 775 20
        • Novartis Investigative Site
      • Praha 2, Czech Republic, 128 08
        • Novartis Investigative Site
  • France
      • Angers Cedex 02, France, 49055
        • Novartis Investigative Site
      • Bordeaux, France, 33076
        • Novartis Investigative Site
      • Creteil, France, 94010
        • Novartis Investigative Site
      • La Roche sur Yon cedex 9, France, 85925
        • Novartis Investigative Site
      • Le Mans Cedex, France, 72015
        • Novartis Investigative Site
      • Marseille, France, 13273
        • Novartis Investigative Site
      • Nice Cedex 2, France, 06189
        • Novartis Investigative Site
      • Saint Herblain cedex, France, 44805
        • Novartis Investigative Site
      • Toulouse Cedex 9, France, 31059
        • Novartis Investigative Site
      • Villejuif Cedex, France, 94805
        • Novartis Investigative Site
  • Germany
      • Bonn, Germany, 53111
        • Novartis Investigative Site
      • Dresden, Germany, 01307
        • Novartis Investigative Site
      • Erlangen, Germany, 91054
        • Novartis Investigative Site
      • Frankfurt, Germany, 60389
        • Novartis Investigative Site
      • Fulda, Germany, 36043
        • Novartis Investigative Site
      • Mainz, Germany, 55131
        • Novartis Investigative Site
      • Muenchen, Germany, 80637
        • Novartis Investigative Site
      • Ravensburg, Germany, 88214
        • Novartis Investigative Site
      • Ulm, Germany, 89081
        • Novartis Investigative Site
  • Hong Kong
      • Hong Kong SAR, Hong Kong
        • Novartis Investigative Site
  • Hungary
      • Budapest, Hungary, 1134
        • Novartis Investigative Site
      • Debrecen, Hungary, 4032
        • Novartis Investigative Site
      • Szolnok, Hungary, H-5000
        • Novartis Investigative Site
  • Israel
      • Ramat Gan, Israel, 5266202
        • Novartis Investigative Site
      • Tel Aviv, Israel, 6423906
        • Novartis Investigative Site
  • Italy
    • FE
      • Cona, FE, Italy, 44100
        • Novartis Investigative Site
    • GE
      • Genova, GE, Italy, 16132
        • Novartis Investigative Site
    • MB
      • Monza, MB, Italy, 20900
        • Novartis Investigative Site
    • ME
      • Messina, ME, Italy, 98158
        • Novartis Investigative Site
    • MI
      • Milano, MI, Italy, 20141
        • Novartis Investigative Site
  • Japan
      • Osaka, Japan, 540-0006
        • Novartis Investigative Site
      • Osaka, Japan, 537-8511
        • Novartis Investigative Site
    • Aichi
      • Nagoya, Aichi, Japan, 464-8681
        • Novartis Investigative Site
      • Nagoya-city, Aichi, Japan, 467-8602
        • Novartis Investigative Site
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 135-8550
        • Novartis Investigative Site
    • Kanagawa
      • Isehara-city, Kanagawa, Japan, 259-1193
        • Novartis Investigative Site
      • Kawasaki-city, Kanagawa, Japan, 216-8511
        • Novartis Investigative Site
      • Yokohama, Kanagawa, Japan, 241-8515
        • Novartis Investigative Site
    • Kumamoto
      • Kumamoto City, Kumamoto, Japan, 860-8556
        • Novartis Investigative Site
    • Osaka
      • Suita-city, Osaka, Japan, 565-0871
        • Novartis Investigative Site
    • Tokyo
      • Koto, Tokyo, Japan, 135-8550
        • Novartis Investigative Site
  • Korea, Republic of
    • Korea
      • Seoul, Korea, Korea, Republic of, 05505
        • Novartis Investigative Site
      • Seoul, Korea, Korea, Republic of, 06351
        • Novartis Investigative Site
      • Seoul, Korea, Korea, Republic of, 03080
        • Novartis Investigative Site
  • Netherlands
      • Breda, Netherlands, 4819 EV
        • Novartis Investigative Site
      • Rotterdam, Netherlands, 3075 EA
        • Novartis Investigative Site
  • Russian Federation
      • St. Petersburg, Russian Federation, 197758
        • Novartis Investigative Site
    • Russia
      • St.- Petersburg, Russia, Russian Federation, 197022
        • Novartis Investigative Site
  • Singapore
      • Singapore, Singapore, 119228
        • Novartis Investigative Site
  • South Africa
      • Johannesburg, South Africa, 2196
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28034
        • Novartis Investigative Site
      • Madrid, Spain, 28007
        • Novartis Investigative Site
      • Madrid, Spain, 28033
        • Novartis Investigative Site
      • Madrid, Spain, 28040
        • Novartis Investigative Site
      • Zaragoza, Spain, 50009
        • Novartis Investigative Site
    • Andalucia
      • Cordoba, Andalucia, Spain, 14004
        • Novartis Investigative Site
      • Malaga, Andalucia, Spain, 29010
        • Novartis Investigative Site
      • Sevilla, Andalucia, Spain, 41013
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08036
        • Novartis Investigative Site
      • Barcelona, Catalunya, Spain, 08003
        • Novartis Investigative Site
      • Hospitalet de LLobregat, Catalunya, Spain, 08907
        • Novartis Investigative Site
    • Comunidad Valenciana
      • Valencia, Comunidad Valenciana, Spain, 46010
        • Novartis Investigative Site
      • Valencia, Comunidad Valenciana, Spain, 46009
        • Novartis Investigative Site
    • Galicia
      • A Coruna, Galicia, Spain, 15009
        • Novartis Investigative Site
    • Santa Cruz de Tenerife
      • La Laguna, Santa Cruz de Tenerife, Spain, 38320
        • Novartis Investigative Site
  • Taiwan
      • New Taipei City, Taiwan, 23561
        • Novartis Investigative Site
      • Taipei, Taiwan, 10048
        • Novartis Investigative Site
    • Taoyuan/ Taiwan ROC
      • Kuei-Shan Chiang, Taoyuan/ Taiwan ROC, Taiwan, 33305
        • Novartis Investigative Site
  • United Kingdom
      • Glasgow - Scotland, United Kingdom, G12 OYN
        • Novartis Investigative Site
      • London, United Kingdom
        • Novartis Investigative Site
      • Wirral, United Kingdom, CH63 3JY
        • Novartis Investigative Site
    • Kent
      • Maidstone, Kent, United Kingdom, M16 9QQ
        • Novartis Investigative Site
  • United States
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Ironwood Cancer and Research Centers SC
      • Phoenix, Arizona, United States
        • Arizona Oncology Associates Dept of Oncology
    • Arkansas
      • Fayetteville, Arkansas, United States, 72703
        • Highlands Oncology Group Dept of Highlands Oncology Grp
    • California
      • Greenbrae, California, United States, 94904
        • California Cancer Care Marian Speciality
    • Colorado
      • Greenwood Village, Colorado, United States
        • Rocky Mountain Cancer Centers RMCC Hale Pkwy
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center & Research Institute SC
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University School of Medicine/Winship Cancer Institute Dept.of WinshipCancerInst. (2)
      • Marietta, Georgia, United States, 30060
        • Northwest Georgia Oncology Center NW Georgia Onc
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center Univ Kansas 2
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Norton Healthcare, Inc.
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School of Medicine Regulatory
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center Unv Nebraska Med Ctr (2)
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • University of New Mexico Cancer Research Center Dept of Univ New Mexico
    • New York
      • Troy, New York, United States, 12180
        • New York Oncology Hematology, P.C. Dept. of New York Oncology. PC
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State Comprehensive Cancer Center/James Cancer Hospital SC-1
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center OUHSC 2
    • Oregon
      • Portland, Oregon, United States, 97210
        • Northwest Cancer Specialists Vancouver Loc
    • Texas
      • Dallas, Texas, United States, 75246
        • Baylor Health Care System/Sammons Cancer Center Baylor Texas Oncology
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center Harry Hines
      • San Antonio, Texas, United States, 78229
        • Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio
    • Virginia
      • Reston, Virginia, United States, 20190
        • Medical Oncology & Hematology Associates of Northern VA Med Onc Hem Northern VA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Breast cancer that is locally advanced or metastatic
  • HER2 negative disease, and a known hormone receptor status - ER/PgR (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
  • Patient has symptomatic CNS metastases
  • Concurrent malignancy or malignancy within 3 years of study enrollment
  • Hematopoietic colony-stimulating growth factors or radiation within 2-4 weeks prior to starting study drug
  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BKM120 and paclitaxel
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received study drug plus paclitaxel.
Drug: Paclitaxel
intravenous paclitaxel 80 mg/m2 per week given until progression
Other Names:
  • Taxol
Drug: BKM120
Buparlisib (BKM120) were supplied as 100 mg and 50 mg hard gelatin capsules. Buparlisib was dosed on a flat scale of mg/day and was not adjusted to body weight or body surface area.
Other Names:
  • Buparlisib
Active Comparator: Placebo and paclitaxel
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received placebo plus paclitaxel.
Drug: Paclitaxel
intravenous paclitaxel 80 mg/m2 per week given until progression
Other Names:
  • Taxol
Drug: BKM120 matching placebo

Buparlisib maching plaxcebo were supplied as 100 mg and 50 mg hard gelatin capsules.

Buparlisib placebo was dosed on a flat scale of mg/day and was not adjusted to body weight or body surface area.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)Assessed by Local Investigator's Assessment (Phase ll)
Time Frame: Every 8 weeks from randomization until disease progression up to 10 months after futility was analyzed
PFS was 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. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Every 8 weeks from randomization until disease progression up to 10 months after futility was analyzed

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival by Kaplan-Meier Estimate (Phase ll)
Time Frame: every 3 months until death, lost to follow-up, or withdrawal of consent to survival follow-up, up to 10 months after futility was analyzed
Overall survival (OS) was 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 contact.
every 3 months until death, lost to follow-up, or withdrawal of consent to survival follow-up, up to 10 months after futility was analyzed
Overall Response Rate (Phase ll)
Time Frame: every 8 weeks after randomization Up to 3 months after end of Treatment
Percentage of patients with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST v1.1. According to this criteria, CR = at least two determinations of CR at least 4 weeks apart before progression; PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
every 8 weeks after randomization Up to 3 months after end of Treatment
Duration of Response (Phase Lll)
Time Frame: every 8 weeks after randomization Up to 3 months after end of Treatment
time from the date of the first documented response (CR or PR, which had to be confirmed subsequently) to the date of the first radiologically documented disease progression or death due to disease
every 8 weeks after randomization Up to 3 months after end of Treatment
Time to Response (Phase Lll)
Time Frame: every 8 weeks after randomization Up to 3 months after end of Treatment
time from date of randomization until first documented response (CR or PR, which has to be confirmed subsequently).
every 8 weeks after randomization Up to 3 months after end of Treatment
Clinical Benefit Rate (CBR) (Phase ll)
Time Frame: every 8 weeks after randomization Up to 3 months after end of Treatment
CBR was defined as the percentage of patients with an overall response of CR or PR or SD or non-CR/non-PD lasting more than 24 weeks based on local Investigator's assessment according to RECIST v1.1.
every 8 weeks after randomization Up to 3 months after end of Treatment
Plasma Concentration-time Profiles of BKM120 - Pharmacokinetics (PK) (Phase Lll)
Time Frame: Cycle 1 day 1, 15, 16, 22 and Cycle 2 day 1.
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.
Time to Definitive Deterioration of ECOG Performance Status (Phase Lll)
Time Frame: every 4 weeks
Time to definitive deterioration of the ECOG performance status from baseline
every 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2012

Primary Completion (Actual)

June 1, 2015

Study Completion (Actual)

June 1, 2015

Study Registration Dates

First Submitted

April 4, 2012

First Submitted That Met QC Criteria

April 4, 2012

First Posted (Estimate)

April 6, 2012

Study Record Updates

Last Update Posted (Actual)

March 9, 2017

Last Update Submitted That Met QC Criteria

January 27, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CBKM120F2202
  • 2011-005932-24 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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