LDK378 in Adult Patients With ALK-activated NSCLC Previously Treated With Chemotherapy and Crizotinib
- Registration Number
- NCT01685060
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
A single-arm, open-label, multicenter, phase II study. Treatment with LDK378 750 mg qd continued until the patient experienced unacceptable toxicity that precluded further treatment, discontinued treatment at the discretion of the investigator or patient, started a new anti-cancer therapy and/or died. LDK378 could be 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. In these patients tumor assessment would continue as per the schedule of assessments until treatment with LDK378 was permanently discontinued. 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 140
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description LDK378 LDK378 Patients treated with ceritinib/LDK378 750 mg once-daily, fasted
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) to LDK378 Per Investigator Assessment 6 cycles of 28 days up to 24 weeks ORR per RECIST 1.1 calculated as the percentage of patients with a best overall confirmed response defined as complete response or partial response (CR+PR) as assessed by 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 1. 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 Duration of Response (DOR) by Investigator 6 cycles of 28 days up to 24 weeks DOR, calculated as the time from the date of the first confirmed CR or PR to the first documented progression or death due to any cause, by 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 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Progression-free Survival (PFS) Per Investigator 6 cycles of 28 days up to 24 weeks PFS, defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had no event or when the patient received any further anticancer therapy in the absence of disease progression, progression-free survival was censored at the date of last adequate tumor assessment.
Overall Intracranial Response Rate (OIRR) Per Investigator 6 cycles of 28 days up to 24 weeks OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.
ORR Per Blinded Independent Review Committee (BIRC) Assessment 6 cycles of 28 days up to 24 weeks ORR (CR+PR) by BIRC is calculated as the percentage of patients with a best overall confirmed response defined as complete response or partial response (CR+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 1. 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) by BIRC 6 cycles of 28 days up to 24 weeks DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to underlying cancer, by BIRC (Blinded Imaging Review Committee). 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 1. 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) 6 cycles of 28 days up to 24 weeks DCR was calculated as the percentage of patients with best overall response of CR, PR, SD, or non-CR non-PD (NCRNPD), per RECIST 1.1 by 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 1. PR: 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. Non-CR/Non-PD (NCRNPD): refers to best overall responses that are neither CR nor PD per RECIST 1.1 criteria for patients with non-measurable disease only at baseline.
Time to Response (TTR) Per Investigator 6 cycles of 28 days up to 24 weeks TTR is the time from date of start of treatment to the first CR or PR observed which were confirmed afterwards.
Time to Response (TTR) Per BIRC 6 cycles of 28 days up to 24 weeks TTR is the time from date of start of treatment to the first CR or PR observed which are confirmed afterwards.
Progression-free Survival (PFS) Per BIRC 6 cycles of 28 days up to 24 weeks PFS, defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had no event or when the patient received any further anticancer therapy in the absence of disease progression, progression-free survival was censored at the date of last adequate tumor assessment.
Overall Survival (OS) 6 cycles of 28 days up to 24 weeks OS, defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last known date patient alive.
Overall Intracranial Response Rate (OIRR) Per BIRC 6 cycles of 28 days up to 24 weeks OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.
Trial Locations
- Locations (18)
City of Hope National Medical Center Dept of Oncology 2
🇺🇸Duarte, California, United States
University of California at San Diego, Moores Cancer Ctr SC
🇺🇸San Diego, California, United States
Stanford University Medical Center Stanford Cancer Center(2)
🇺🇸Stanford, California, United States
University of Chicago Medical Center SC
🇺🇸Chicago, Illinois, United States
Emory University School of Medicine/Winship Cancer Institute Dept of Oncology
🇺🇸Atlanta, Georgia, United States
Levine Cancer Institute SC 1
🇺🇸Charlotte, North Carolina, United States
Maryland Oncology Hematology, P.A. SC
🇺🇸Rockville, Maryland, United States
Sarah Cannon Research Institute Drug Ship - 4
🇺🇸Nashville, Tennessee, United States
U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office
🇺🇸Dallas, Texas, United States
Novartis Investigative Site
🇬🇧London, United Kingdom
University of Wisconsin Univ Wisc 2
🇺🇸Madison, Wisconsin, United States
Seattle Cancer Care Alliance SC-1
🇺🇸Seattle, Washington, United States
University of Colorado Hospital SC
🇺🇸Aurora, Colorado, United States
Cancer Center of Kansas Dept of CCK
🇺🇸Wichita, Kansas, United States
University of Kansas Cancer Center DeptofUofKansas CancerCenter-2
🇺🇸Kansas City, Kansas, United States
University of California at Los Angeles Reg-5
🇺🇸Los Angeles, California, United States
Massachusetts General Hospital Mass General
🇺🇸Boston, Massachusetts, United States
Highlands Oncology Group Dept of Highlands Oncology Grp
🇺🇸Fayetteville, Arkansas, United States