Safety and Efficacy of BKM120 in Patients With Metastatic Non-small Cell Lung Cancer
- Registration Number
- NCT01297491
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 63
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Squamous BKM120 100mg qd BKM120 Diagnosed patients with non-small cell lung cancer (NSCLC) that progressed after one prior, platinum-based chemotherapy line for metastatic disease. Non-Squamous BKM120 100mg qd BKM120 Diagnosed patients with non-squamous NSCLC that progressed after one or two prior antineoplastic therapy lines for metastatic disease.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) Rate as Per Investigator Local Review Measured Using RECIST 1.1 of Patients at Week 12 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.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Using Kaplan-Meier Estimates Every 8 weeks up to 24 months 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 Every 6 weeks up to 24 months 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) Every 6 weeks up tp 24 months 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) Every 6 weeks up to 24 months 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) Every 6 weeks up to 24 months 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.
Trial Locations
- Locations (33)
Washington University School of Medicine Washington University (16)
🇺🇸St. Louis, Missouri, United States
Fallon Clinic at Worcester Medical Center Fallon Clinic Worcester Med
🇺🇸Worcester, Massachusetts, United States
Baylor Health Care System/Sammons Cancer Center Baylor Texas Oncology
🇺🇸Dallas, Texas, United States
Texas Oncology South Texas Oncology
🇺🇸Dallas, Texas, United States
University of Chicago Medical Center Unvi Chi
🇺🇸Chicago, Illinois, United States
MetroHealth Medical Center Dept.ofMetroHealthMedCtr.(2)
🇺🇸Cleveland, Ohio, United States
Emory University School of Medicine/Winship Cancer Institute Emory 2
🇺🇸Atlanta, Georgia, United States
Rocky Mountain Cancer Centers Dept. of Rocky Mountain Cancer
🇺🇸Greenwood Village, Colorado, United States
Ironwood Cancer and Research Centers SC
🇺🇸Chandler, Arizona, United States
Massachusetts General Hospital Mass General
🇺🇸Boston, Massachusetts, United States
Novartis Investigative Site
🇬🇧Manchester, United Kingdom
Hematology Oncology Associates of Northern New Jersey PA DeptofHem-OncofNorthern NJ (2)
🇺🇸Morristown, New Jersey, United States
Memorial Sloan Kettering Cancer Center Sloan Kettering
🇺🇸NY, New York, United States
University of Oklahoma Health Sciences Center Dept. of Oklahoma Univ. HSC
🇺🇸Oklahoma City, Oklahoma, United States
Rush University Medical Center SC
🇺🇸Chicago, Illinois, United States
Duke University Medical Center Duke 2
🇺🇸Durham, North Carolina, United States
University of Colorado Univ CO
🇺🇸Aurora, Colorado, United States
Karmanos Cancer Institute Wayne St Karmanos
🇺🇸Detroit, Michigan, United States
Overlook Hospital - Carol G Simon Cancer Center Carol G Simon
🇺🇸Summit, New Jersey, United States
Roswell Park Cancer Institute Rosewell
🇺🇸Buffalo, New York, United States
Virginia Oncology Associates VOA - Lake Wright (2)
🇺🇸*see Various Departments*, Virginia, United States
Northwest Cancer Specialists Compass Oncology -BKM
🇺🇸Portland, Oregon, United States
U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office
🇺🇸Dallas, Texas, United States
University of Pittsburgh Medical Center SC-2
🇺🇸Pittsburgh, Pennsylvania, United States
Arizona Oncology Associates Tucson (Rudasill & La Cholla)
🇺🇸Phoenix, Arizona, United States
Mayo Clinic - Arizona Mayo Scottsdale AZ
🇺🇸Scottsdale, Arizona, United States
Highlands Oncology Group Dept of Highlands Oncology Grp
🇺🇸Fayetteville, Arkansas, United States
University of California at San Diego, Moores Cancer Ctr SC
🇺🇸San Diego, California, United States
Cedars Sinai Medical Center Dept.of Cedars-Sinai Med. Ctr.
🇺🇸Los Angeles, California, United States
H. Lee Moffitt Cancer Center & Research Institute H Lee Moffitt
🇺🇸Tampa, Florida, United States
Medical University of South Carolina MUSC
🇺🇸Charleston, South Carolina, United States
University of Wisconsin Univ WIsc 2
🇺🇸Madison, Wisconsin, United States
University of Kansas Cancer Center Univ of KS
🇺🇸Kansas City, Kansas, United States