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

  Show 92 Study Locations
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