Safety and Efficacy of BKM120 in Patients With Metastatic Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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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.

Official Title
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An Open Label Two-stage Study of Orally Administered BKM120 in Patients With Metastatic Non-small Cell Lung Cancer With Activated PI3K Pathway

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: BKM120


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Squamous BKM120 100mg qd<br>Diagnosed patients with non-small cell lung cancer (NSCLC) that progressed after one prior, platinum-based chemotherapy line for metastatic disease. | Drug: BKM120<br>* 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.<br>* Other names: Buparlisib;|
| Experimental: Non-Squamous BKM120 100mg qd<br>Diagnosed patients with non-squamous NSCLC that progressed after one or two prior antineoplastic therapy lines for metastatic disease. | Drug: BKM120<br>* 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.<br>* Other names: Buparlisib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) Rate as Per Investigator Local Review Measured Using RECIST 1.1 of Patients at Week 12 | 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. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) Using Kaplan-Meier Estimates | 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. | Every 8 weeks up to 24 months | 
| Overall Response Rate (ORR) Based on Investigator Assessment | 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. | Every 6 weeks up to 24 months | 
| Disease Control Rate (DCR) | 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. | Every 6 weeks up tp 24 months | 
| Time to Response (TTR) | 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. | Every 6 weeks up to 24 months | 
| Duration of Response (DoR) | 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. | Every 6 weeks up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, PI3K