Safety and Efficacy of BKM120 in Patients With Metastatic Non-small Cell Lung Cancer (BASALT-1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01297491
First received: February 11, 2011
Last updated: December 31, 2015
Last verified: December 2015
  Purpose
The purpose of this two-stage phase II study is to assess the efficacy of BKM120, as measured by determining the progression free survival (PFS), in patients with pretreated metastatic Non-small Cell Lung Cancer (NSCLC) that exhibits PI3K pathway activation. BKM120 will be investigated in two groups of NSCLC patients according to the histology of the cancer: squamous and non-squamous.

Condition Intervention Phase
Non-small Cell Lung Cancer
Drug: BKM120
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Two-stage Study of Orally Administered BKM120 in Patients With Metastatic Non-small Cell Lung Cancer With Activated PI3K Pathway

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Progression Free Survival (PFS) Rate as Per Investigator Local Review Measured Using RECIST 1.1 of Patients at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

    PFS rate was defined as the percentage of participants who were progression free at 12 weeks. Participants were considered as a "success" for PFS rate evaluated at 12 weeks if they presented an overall response at their 2nd post-baseline tumor assessment.The enrollment into the study in either histology group would stop for futility if a PFS rate <50% at 12 weeks was observed.

    No statistical analysis was planned for this primary outcome. The results of the primary objective was based on the data from the interim analysis that took place at the cut off dates: 10-Apr-2013 for non-squamous and 08-Jan-2014 for squamous group.



Secondary Outcome Measures:
  • Overall Survival (OS) Using Kaplan-Meier Estimates [ Time Frame: Every 8 weeks up to 24 months ] [ Designated as safety issue: No ]
    OS was defined as the time from start of study drug (Stage 1) until death from any cause. If a patient was not known to have died, survival was censored at the date of last contact.

  • Overall Response Rate (ORR) Based on Investigator Assessment [ Time Frame: Every 6 weeks up to 24 months ] [ Designated as safety issue: No ]
    ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR). Complete response was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. Partial response was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Analyses of response rates were performed based on investigators' assessments (as per RECIST 1.1 criteria). ORR included all patients with and without measurable disease at baseline.

  • Disease Control Rate (DCR) [ Time Frame: Every 6 weeks up tp 24 months ] [ Designated as safety issue: No ]

    DCR defined as the percentage of participants with best overall response of CR or PR or stable disease (SD). Complete response was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. Partial response was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.

    Analyses of response rates were performed based on investigators' assessments (as per RECIST 1.1 criteria). DCR included all participants with and without measurable disease at baseline.


  • Time to Response (TTR) [ Time Frame: Every 6 weeks up to 24 months ] [ Designated as safety issue: No ]
    TTR for a participant was defined as the time from the first treatment date to the date of first documented confirmed CR or PR evaluation. The date of event was defined as the date of response that was first determined and not using the date the response was confirmed.

  • Duration of Response (DoR) [ Time Frame: Every 6 weeks up to 24 months ] [ Designated as safety issue: No ]
    DoR was defined as the elapsed time between the date of first documented CR or PR response (not the date of confirmed response) and the following date of event defined as the first documented progression or death due to underlying cancer.


Enrollment: 63
Study Start Date: May 2011
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Squamous BKM120 100mg qd
Diagnosed patients with non-small cell lung cancer (NSCLC) that progressed after one prior, platinum-based chemotherapy line for metastatic disease.
Drug: BKM120
Buparlisib was supplied as 10mg or 50mg capsules. It was administered on a continuous once daily dosing schedule at a dose of 100 mg. The patient was dosed on a flat scale of mg/day and not adjusted to body weight or body surface area.
Other Name: Buparlisib
Experimental: Non-Squamous BKM120 100mg qd
Diagnosed patients with non-squamous NSCLC that progressed after one or two prior antineoplastic therapy lines for metastatic disease.
Drug: BKM120
Buparlisib was supplied as 10mg or 50mg capsules. It was administered on a continuous once daily dosing schedule at a dose of 100 mg. The patient was dosed on a flat scale of mg/day and not adjusted to body weight or body surface area.
Other Name: Buparlisib

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed NSCLC with activated PI3K pathway
  • Progressive disease after prior systemic antineoplastic treatment(s) for advanced NSCLC
  • Archival or fresh tumor biopsy must be available for profiling
  • Measurable and/or non-measurable disease as per RECIST 1.1 criteria
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Adequate organ function as assessed by laboratory tests

Exclusion Criteria:

  • Patient has received previous treatment with PI3K inhibitors
  • Patient with squamous NSCLC has received more than one line of chemotherapy treatment for metastatic disease; patient with non-squamous NSCLC has received more than two lines of systemic antineoplastic treatment for metastatic disease
  • Uncontrolled or symptomatic CNS metastases
  • Concurrent use of any other approved or investigational antineoplastic agent
  • Radiotherapy ≤ 28 days prior to starting study drug
  • Major surgery within 28 days prior to starting study drug
  • History of clinically significant cardiac dysfunction, mood disorders, or poorly controlled diabetes mellitus
  • Current treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes
  • Impairment of gastrointestinal (GI) function
  • Chronic treatment with steroids or another immunosuppressive agent.
  • Concurrent severe and/or uncontrolled medical condition
  • Currently receiving Warfarin or another coumarin derivative
  • Known history of HIV infection
  • Sensory neuropathy with functional impairment (CTC grade 2 neuropathy, regardless of causality)
  • Pregnancy, lactation, or breastfeeding
  • Woman of child-bearing potential

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01297491

  Hide Study Locations
Locations
United States, Arizona
Ironwood Cancer and Research Centers SC
Chandler, Arizona, United States, 85224
Arizona Oncology Associates Tucson (Rudasill & La Cholla)
Phoenix, Arizona, United States
Mayo Clinic - Arizona Mayo Scottsdale AZ
Scottsdale, Arizona, United States, 85259
United States, Arkansas
Highlands Oncology Group Dept of Highlands Oncology Grp
Fayetteville, Arkansas, United States, 72703
United States, California
Cedars Sinai Medical Center Dept.of Cedars-Sinai Med. Ctr.
Los Angeles, California, United States, 90048
University of California at San Diego, Moores Cancer Ctr SC
San Diego, California, United States, 92103
United States, Colorado
University of Colorado Univ CO
Aurora, Colorado, United States, 80045
Rocky Mountain Cancer Centers Dept. of Rocky Mountain Cancer
Greenwood Village, Colorado, United States, 80218
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute H Lee Moffitt
Tampa, Florida, United States, 33612
United States, Georgia
Emory University School of Medicine/Winship Cancer Institute Emory 2
Atlanta, Georgia, United States, 30322
United States, Illinois
Rush University Medical Center SC
Chicago, Illinois, United States, 60612
University of Chicago Medical Center Unvi Chi
Chicago, Illinois, United States, 60637
United States, Kansas
University of Kansas Cancer Center Univ of KS
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Massachusetts General Hospital Mass General
Boston, Massachusetts, United States, 02114
Fallon Clinic at Worcester Medical Center Fallon Clinic Worcester Med
Worcester, Massachusetts, United States, 01608
United States, Michigan
Karmanos Cancer Institute Wayne St Karmanos
Detroit, Michigan, United States, 48201
United States, Missouri
Washington University School of Medicine Washington University (16)
St. Louis, Missouri, United States, 63110
United States, New Jersey
Hematology Oncology Associates of Northern New Jersey PA DeptofHem-OncofNorthern NJ (2)
Morristown, New Jersey, United States, 07962
Overlook Hospital - Carol G Simon Cancer Center Carol G Simon
Summit, New Jersey, United States, 07901
United States, New York
Roswell Park Cancer Institute Rosewell
Buffalo, New York, United States, 14263
Memorial Sloan Kettering Cancer Center Sloan Kettering
NY, New York, United States, 90033
United States, North Carolina
Duke University Medical Center Duke 2
Durham, North Carolina, United States, 27710
United States, Ohio
MetroHealth Medical Center Dept.ofMetroHealthMedCtr.(2)
Cleveland, Ohio, United States, 44109-1998
United States, Oklahoma
University of Oklahoma Health Sciences Center Dept. of Oklahoma Univ. HSC
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Northwest Cancer Specialists Compass Oncology -BKM
Portland, Oregon, United States, 97210
United States, Pennsylvania
University of Pittsburgh Medical Center SC-2
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Medical University of South Carolina MUSC
Charleston, South Carolina, United States, 29425
United States, Texas
Baylor Health Care System/Sammons Cancer Center Baylor Texas Oncology
Dallas, Texas, United States, 75246
Texas Oncology South Texas Oncology
Dallas, Texas, United States, 75251
U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office
Dallas, Texas, United States, 75390-9151
United States, Virginia
Virginia Oncology Associates VOA - Lake Wright (2)
*see Various Departments*, Virginia, United States, 23502
United States, Wisconsin
University of Wisconsin Univ WIsc 2
Madison, Wisconsin, United States, 53792
Argentina
Novartis Investigative Site
Rio Negro, Viedma, Argentina, 8500
Novartis Investigative Site
Buenos Aires, Argentina, C1050AAK
Novartis Investigative Site
Cordoba, Argentina, X5002AOQ
Belgium
Novartis Investigative Site
Brussel, Belgium, 1090
Novartis Investigative Site
Charleroi, Belgium, 6000
Novartis Investigative Site
Genk, Belgium, 3600
Novartis Investigative Site
Leuven, Belgium, 3000
Novartis Investigative Site
Libramont, Belgium, 6800
Brazil
Novartis Investigative Site
Salvador, BA, Brazil, 41253-190
Novartis Investigative Site
Rio de Janeiro, RJ, Brazil, 20230-130
Novartis Investigative Site
Florianopolis, SC, Brazil, 88034-000
Novartis Investigative Site
Barretos, SP, Brazil, 14784-400
Novartis Investigative Site
São Paulo, SP, Brazil, 01246-000
Canada, British Columbia
Novartis Investigative Site
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 1Z5
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H2X 3J4
France
Novartis Investigative Site
Caen Cedex, France, 14021
Novartis Investigative Site
Creteil, France, 94000
Novartis Investigative Site
Marseille cedex 20, France, 13915
Novartis Investigative Site
Rennes, France, F-35043
Novartis Investigative Site
Villejuif Cedex, France, 94805
Germany
Novartis Investigative Site
Berlin, Germany, 13125
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Gauting, Germany, 82131
Novartis Investigative Site
Grosshansdorf, Germany, 22927
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Koeln, Germany, 51109
Novartis Investigative Site
Nuernberg, Germany, 90419
Novartis Investigative Site
Oldenburg, Germany, 26121
Novartis Investigative Site
Recklinghausen, Germany, 45657
Hong Kong
Novartis Investigative Site
Hongkong, Hong Kong
Hungary
Novartis Investigative Site
Budapest, Hungary, 1121
Novartis Investigative Site
Budapest, Hungary, 1125
Novartis Investigative Site
Deszk, Hungary, 6772
Novartis Investigative Site
Mátraháza, Hungary, 3233
Novartis Investigative Site
Szolnok, Hungary, H-5000
Italy
Novartis Investigative Site
Avellino, AV, Italy, 83100
Novartis Investigative Site
Genova, GE, Italy, 16132
Novartis Investigative Site
Milano, MI, Italy, 20133
Novartis Investigative Site
Milano, MI, Italy, 20141
Novartis Investigative Site
Parma, PR, Italy, 43100
Novartis Investigative Site
Udine, UD, Italy, 33100
Japan
Novartis Investigative Site
Kurashiki, Okayama, Japan, 710-8602
Novartis Investigative Site
Koto, Tokyo, Japan, 135-8550
Netherlands
Novartis Investigative Site
Maastricht, Netherlands, 6229 HX
Singapore
Novartis Investigative Site
Singapore, Singapore, 169610
Spain
Novartis Investigative Site
Sabadell, Barcelona, Spain, 08208
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Mataro, Cataluña, Spain, 08301
Novartis Investigative Site
Alicante, Comunidad Valenciana, Spain, 03010
Taiwan
Novartis Investigative Site
Tainan 704, Taiwan ROC, Taiwan, 704
Novartis Investigative Site
Taipei, Taiwan ROC, Taiwan, 100
Thailand
Novartis Investigative Site
Bangkok, Thailand, 10700
Novartis Investigative Site
Chiang Mai, Thailand, 50200
Turkey
Novartis Investigative Site
Altunizade, Turkey, 34662
Novartis Investigative Site
Izmir, Turkey, 35040
United Kingdom
Novartis Investigative Site
Northwood, Middlesex, United Kingdom, HA6 2RN
Novartis Investigative Site
Leicester, United Kingdom, LE1 5WW
Novartis Investigative Site
London, United Kingdom, SE1 9RT
Novartis Investigative Site
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Publications:
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01297491     History of Changes
Other Study ID Numbers: CBKM120D2201  2010-024011-14 
Study First Received: February 11, 2011
Results First Received: October 30, 2015
Last Updated: December 31, 2015
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: National Institute of Health
Japan: Pharmaceuticals and Medical Devices Agency
Singapore: Health Sciences Authority
Spain: Spanish Agency of Medicines
Taiwan: Department of Health
Thailand: Food and Drug Administration
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
NSCLC
PI3K

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms

ClinicalTrials.gov processed this record on February 04, 2016