LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer
- Registration Number
- NCT01685138
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
A single-arm, open-label, two-stage multicenter, phase II study. Patients were pre-screened for ALK positive status. Treatment with LDK378 at 750 mg qd was continued until the patient experienced unacceptable toxicity that precluded further treatment, discontinued treatment at the discretion of the investigator or patient, started a new anticancer therapy and/or died. LDK378 was continued beyond RECIST defined progressive disease (PD) as assessed by the investigator, if in the judgment of the investigator, there was evidence of clinical benefit. Patients who discontinued the study medication in the absence of progression continued to be followed for tumor assessment until the time of PD as assessed by the investigator. Male and female patients aged 18 or over with ALK-rearranged non-small cell cancer (NSCLC) were screened for eligibility. Patients had to have received no prior crizotinib, and had to be chemotherapy-naïve or been pretreated with cytotoxic chemotherapy (up to three prior lines).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 124
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description LDK378 (Ceritinib) LDK378 Participants on this arm took oral LDK378 750 mg once daily.
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) by Investigator Assessment every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years ORR per RECIST 1.1 calculated as the percentage of participants with a best overall response (OR) defined as complete response (CR) or partial response (PR) as assessed by the investigator. CR: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. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
- Secondary Outcome Measures
Name Time Method ORR by Blinded Independent Review Committee (BIRC) every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years ORR per RECIST 1.1 calculated as the percentage of participants with a best overall response (OR) defined as complete response (CR) or partial response (PR) as assessed by BIRC. CR: 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. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Duration of Response (DOR) as Per Investigator every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to any cause, by investigator assessment per RECIST 1.1. CR: 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. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Duration of Response (DOR) as Per BIRC every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to any cause, by BIRC assessment per RECIST 1.1. CR: 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. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Disease Control Rate (DCR) as Per Investigator and BIRC every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years DCR per RECIST 1.1 is the percentage of participants with best overall response of CR, PR, stable disease (SD) or Non-CR/Non-PD. CR: Disappearance of all non-nodal target lesions. Also, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions that would qualify for PD. PD: At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm.
Overall Survival (OS) Time from the date of first dose of LDK378 to the date of death due to any cause up to 5 years OS, defined as time from first dose of LDK378 to death due to any cause
Time to Response (TTR) as Per Investigator every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by investigator. This was only on participants with confirmed CR or PR. CR: 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. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time to Response (TTR) as Per BIRC every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by BIRC assessment. This was only on participants with confirmed CR or PR. CR: 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. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Overall Intracranial Response Rate (OIRR) as Per BIRC every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline by BIRC.
Overall Intracranial Response Rate (OIRR) as Per Investigator every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline by investigator.
Progression-free Survival (PFS) Per Investigator and BIRC every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years PFS, defined as time from first dose of LDK378 to progression or death due to any cause, as assessed by investigator and BIRC assessments.
Trial Locations
- Locations (5)
Massachusetts General Hospital Mass Gen 5
🇺🇸Boston, Massachusetts, United States
Washington University School of Medicine Washington University (16)
🇺🇸Saint Louis, Missouri, United States
U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office
🇺🇸Dallas, Texas, United States
Novartis Investigative Site
🇬🇧London, United Kingdom
Sarah Cannon Research Institute Drug Ship - 4
🇺🇸Nashville, Tennessee, United States