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LDK378 in Adult Patients With ALK-activated NSCLC Previously Treated With Chemotherapy and Crizotinib

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01685060
Recruitment Status : Completed
First Posted : September 13, 2012
Results First Posted : May 8, 2017
Last Update Posted : June 19, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE September 4, 2012
First Posted Date  ICMJE September 13, 2012
Results First Submitted Date  ICMJE March 27, 2017
Results First Posted Date  ICMJE May 8, 2017
Last Update Posted Date June 19, 2017
Actual Study Start Date  ICMJE November 26, 2012
Actual Primary Completion Date March 29, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2017)
Overall Response Rate (ORR) to LDK378 Per Investigator Assessment [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 12, 2012)
Overall response rate (ORR) to LDK378 by investigator assessment [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
ORR per RECIST v1.1 calculated as the proportion of patients with a best overall response defined as complete response or partial response (CR+PR) as assessed by investigator
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2017)
  • ORR Per Blinded Independent Review Committee (BIRC) Assessment [ Time Frame: 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 Investigator [ Time Frame: 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.
  • Duration of Response (DOR) by BIRC [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 Investigator [ Time Frame: 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.
  • Progression-free Survival (PFS) Per BIRC [ Time Frame: 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 [ Time Frame: 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.
  • Overall Intracranial Response Rate (OIRR) Per BIRC [ Time Frame: 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.
  • Overall Survival (OS) [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2012)
  • Duration of response (DOR) [ Time Frame: 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 investigator and BIRC (Blinded Imaging Review Committee)
  • Disease control rate (DCR) [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    DCR, calculated as the proportion of patients with best overall response of CR, PR, or SD, by investigator and BIRC
  • Time to Response (TTR) [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by investigator and BIRC
  • ORR by BIRC assessment [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    ORR (CR+PR) per RECIST v1.1 as assessed by BIRC
  • Safety profile [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    Adverse events and laboratory abnormalities
  • Progression-free survival (PFS) [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    PFS, defined as time from first dose of LDK378 to progression or death due to any cause, as assessed by BIRC and investigator assessment
  • Overall Survival (OS) [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    OS, defined as time from first dose of LDK378 to death due to any cause
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE LDK378 in Adult Patients With ALK-activated NSCLC Previously Treated With Chemotherapy and Crizotinib
Official Title  ICMJE A Phase II, Multicenter, Single-arm Study of Oral LDK378 in Adult Patients With ALK-activated Non-small Cell Lung Cancer Previously Treated With Chemotherapy and Crizotinib
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE Drug: LDK378
Ceritinib/LDK378 was supplied as 150 mg hard gelatin capsules and were administered orally, once-daily at a dose of 750 mg on a continuous dosing schedule (5 x 150 mg capsules).
Other Name: Ceritinib
Study Arms  ICMJE Experimental: LDK378
Patients treated with ceritinib/LDK378 750 mg once-daily, fasted
Intervention: Drug: LDK378
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 27, 2017)
140
Original Estimated Enrollment  ICMJE
 (submitted: September 12, 2012)
137
Actual Study Completion Date  ICMJE March 29, 2016
Actual Primary Completion Date March 29, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion critieria:

  • Histologically or cytologically confirmed diagnosis of stage IIIB or IV NSCLC that carries an ALK rearrangement, as per the FDA-approved FISH assay (Abbott Molecular Inc.).
  • Age 18 years or older at the time of informed consent.
  • Patients must have NSCLC that has progressed during therapy with crizotinib or within 30 days of the last dose
  • Patients must have received 1-3 lines of cytotoxic chemotherapy (of which 1 must have been a platinum doublet) to treat their locally advanced or metastatic NSCLC
  • Patients must have a tumor tissue sample available, collected either at the time of diagnosis of NSCLC or any time since.
  • Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 2, except for patients with grade 2 nausea/vomiting and/or grade 2 diarrhea despite optimal supportive therapy who will not be allowed to participate in the study.

Exclusion criteria:

  • Patients with known hypersensitivity to any of the excipients of LDK378.
  • Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
  • History of carcinomatous meningitis.
  • Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years.
  • Clinically significant, uncontrolled heart disease
  • Systemic anti-cancer therapy given after the last dose of crizotinib and prior to starting study drug.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   France,   Germany,   Hong Kong,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Singapore,   Spain,   United Kingdom,   United States
Removed Location Countries Australia,   Belgium,   Sweden
 
Administrative Information
NCT Number  ICMJE NCT01685060
Other Study ID Numbers  ICMJE CLDK378A2201
2012-003432-24 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP