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LDK378 Versus Chemotherapy in ALK Rearranged (ALK Positive) Patients Previously Treated With Chemotherapy (Platinum Doublet) 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: NCT01828112
Recruitment Status : Active, not recruiting
First Posted : April 10, 2013
Results First Posted : July 27, 2017
Last Update Posted : June 11, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE April 2, 2013
First Posted Date  ICMJE April 10, 2013
Results First Submitted Date  ICMJE June 24, 2017
Results First Posted Date  ICMJE July 27, 2017
Last Update Posted Date June 11, 2020
Actual Study Start Date  ICMJE June 28, 2013
Actual Primary Completion Date January 26, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 3, 2017)
Progression Free Survival (PFS) Blinded Independent Review Committee Per Blinded Independent Review Committee (BIRC) [ Time Frame: 'from the date of randomization to the date of first radiologically documented disease progression or death due to any cause up to approximately 24 months ]
PFS is defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause.
Original Primary Outcome Measures  ICMJE
 (submitted: April 9, 2013)
Progression Free Survival (PFS) [ Time Frame: Month 18 ]
PFS which is defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2017)
  • Overall Survival (OS) [ Time Frame: Month 18 ]
    OS is defined as time from date of randomization to date of death due to any cause.
  • Overall Response Rate (ORR) [ Time Frame: Month 18 ]
    ORR is defined as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR); (CR+PR)
  • Duration of Response (DOR) [ Time Frame: Month 18 ]
    DOR is defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to underlying cancer
  • Disease Control Rate (DCR) [ Time Frame: Month 18 ]
    DCR is defined as the proportion of patients with best overall response of CR, PR, or stable disease (SD)
  • Time to Response (TTR) [ Time Frame: Month 18 ]
    TTR is defined as the time from date of randomization to date of first documented response (CR or PR)
  • Patient Reported Outcomes (PRO) [ Time Frame: Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks ]
  • Time to Definitive Deterioration [ Time Frame: from the date of randomization to the date of event for disease related symptoms ]
  • Overall Intracranial Response Rate (OIRR) [ Time Frame: Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks ]
    OIRR is defined as the ORR based on lesions in brain (target, nontarget lesions (and new lesions, if applicable) and calculated as the proportion of patients with a best overall confirmed response of CR or PR in the brain per modified RECIST 1.1* as assessed by BIRC neuroradiologist.
  • Intracranial Disease Control Rate (IDCR) [ Time Frame: Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks ]
    IDCR is defined as the DCR based on lesions in brain (target, non-target lesions (and new lesions, if applicable) and calculated as the proportion of patients with a best overall response of CR or PR or SD (or non-CR/nonPD) in the brain per modified RECIST 1.1* as assessed by BIRC neuro-radiologist.
  • Duration of Intracranial Response (DOIR) [ Time Frame: Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks ]
    DOIR is defined as the DOR based on lesions in brain (target, non-target lesions (and new lesions, if applicable) and calculated from the time of first documented response of CR or PR to the date of the first documented disease progression in the brain or death due to any cause per modified RECIST 1.1* as assessed by BIRC neuro-radiologist.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2013)
  • Overall Survival (OS) [ Time Frame: Month 18 ]
    OS defined as time from date of randomization to date of death due to any cause
  • Overall Response Rate (ORR) [ Time Frame: Month 18 ]
    ORR is defined as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR); (CR+PR)
  • Duration of Response (DOR) [ Time Frame: Month 18 ]
    DOR is defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to underlying cancer
  • Disease Control Rate (DCR) [ Time Frame: Month 18 ]
    DCR is defined as the proportion of patients with best overall response of CR, PR, or stable disease (SD)
  • Time to Response (TTR) [ Time Frame: Month 18 ]
    TTR is defined as the time from date of randomization to date of first documented response (CR or PR)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE LDK378 Versus Chemotherapy in ALK Rearranged (ALK Positive) Patients Previously Treated With Chemotherapy (Platinum Doublet) and Crizotinib
Official Title  ICMJE A Phase III, Multicenter, Randomized, Open-label Study of Oral LDK378 Versus Standard Chemotherapy in Adult Patients With ALK-rearranged (ALK-positive) Advanced Non-small Cell Lung Cancer Who Have Been Treated Previously With Chemotherapy (Platinum Doublet) and Crizotinib
Brief Summary The primary purpose of the study was to compare the antitumor activity of LDK378 vs. chemotherapy in patients previously treated with chemotherapy (platinum doublet) and crizotinib.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Ceritinib
    Ceritinib is the investigational treatment and is referred to as the investigational study drug and was provided as 150 mg hard gelatin capsules for oral use. The dose was 750 mg once daily.
  • Drug: pemetrexed
    Pemetrexed was one of the chemotherapy treatments. Pemetrexed, a reconstituted solution, was intravenously administered over 10 minutes at 500 mg/m2 every 21 days.
  • Drug: docetaxel
    Docetaxel was one of the chemotherapy treatments. Docetaxel, a reconstituted solution, was intravenously administered over 1 hour, at 75 mg/m2 every 21 days.
Study Arms  ICMJE
  • Experimental: Ceritinib
    Patients in this arm received 750 mg of ceritinib.
    Intervention: Drug: Ceritinib
  • Active Comparator: Chemotherapy
    Patients in this arm received chemotherapy of either pemetrexed or docetaxel as determined by BIRC.
    Interventions:
    • Drug: pemetrexed
    • Drug: docetaxel
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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 13, 2020)
231
Original Estimated Enrollment  ICMJE
 (submitted: April 9, 2013)
236
Estimated Study Completion Date  ICMJE September 9, 2022
Actual Primary Completion Date January 26, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patient has a histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive as assessed by the FDA approved Abbott FISH Test.
  2. Patient has stage IIIB or IV diagnosis and must have received one or two prior regimens (including platinum- doublet) of cytotoxic chemotherapy for the treatment of locally advanced or metastatic NSCLC.
  3. Patient has at least one measurable lesion as defined by RECIST 1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation
  4. Patients must have received previous treatment with crizotinib for the treatment of locally advanced or metastatic NSCLC.

Exclusion Criteria:

  1. Patient with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)
  2. Patient with a history of severe hypersensitivity reaction to pemetrexed or docetaxel or any known excipients of these drugs.
  3. Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids within the 2 weeks prior to screening to manage CNS symptoms.
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 Belgium,   Canada,   France,   Germany,   Hong Kong,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Lebanon,   Netherlands,   Portugal,   Russian Federation,   Singapore,   Spain,   Switzerland,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01828112
Other Study ID Numbers  ICMJE CLDK378A2303
2012-005637-36 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

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 June 2020

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