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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 )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non-Small Cell Lung Cancer
Interventions Drug: Ceritinib
Drug: pemetrexed
Drug: docetaxel
Enrollment 231
Recruitment Details 115 patients received ceritinib and 116 received chemotherapy among which 40 patients received pemetrexed, 73 patients received docetaxel, and 3 were not treated (2 patients due to Investigators decision and 1 due to subject/guardian’s decision).
Pre-assignment Details A total of 231 patients were randomized in a 1:1 ratio to the ceritinib arm (n=115) or the chemotherapy arm (n=116).
Arm/Group Title Ceritinib Chemotherapy
Hide Arm/Group Description Ceritinib 750 mg Chemotherapy as determined by BIRC.
Period Title: Overall Study
Started 115 116
Entered Extension Treatment Phase 0 74
Entered Post-treatment Follow-up Phase 7 5
Entered Survival Follow-up Phase 61 19
Discontinued From Study 14 10
Untreated Patients 0 3 [1]
Untreated 0 3
Treated 115 113
Completed 33 [2] 8 [2]
Not Completed 82 108
Reason Not Completed
Adverse Event             6             8
Death             9             5
Physician Decision             5             5
Progressive disease             56             82
Subject/guardian decision             6             8
[1]
untreated = did not receive study drug
[2]
Completed = Ongoing at time of data cut-off of 26-Jan-2016
Arm/Group Title Ceritinib Chemotherapy Total
Hide Arm/Group Description Ceritinib 750 mg Chemotherapy as determined by BIRC. Total of all reporting groups
Overall Number of Baseline Participants 115 116 231
Hide Baseline Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned by randomization.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 115 participants 116 participants 231 participants
53.1  (11.96) 54.4  (11.61) 53.7  (11.78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 116 participants 231 participants
Female
68
  59.1%
61
  52.6%
129
  55.8%
Male
47
  40.9%
55
  47.4%
102
  44.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 116 participants 231 participants
Asian
30
  26.1%
38
  32.8%
68
  29.4%
Black
0
   0.0%
1
   0.9%
1
   0.4%
Caucasian
81
  70.4%
68
  58.6%
149
  64.5%
Other
2
   1.7%
4
   3.4%
6
   2.6%
Unknown
2
   1.7%
5
   4.3%
7
   3.0%
1.Primary Outcome
Title Progression Free Survival (PFS) Blinded Independent Review Committee Per Blinded Independent Review Committee (BIRC)
Hide Description 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.
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
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned by randomization.
Arm/Group Title Ceritinib Chemotherapy
Hide Arm/Group Description:
Ceritinib 750 mg
Chemotherapy as determined by BIRC.
Overall Number of Participants Analyzed 115 116
Median (95% Confidence Interval)
Unit of Measure: Percentage of participants
5.4
(4.1 to 6.9)
1.6
(1.4 to 2.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ceritinib, Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.49
Confidence Interval (2-Sided) 95%
0.36 to 0.67
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS is defined as time from date of randomization to date of death due to any cause.
Time Frame Month 18
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Overall Response Rate (ORR)
Hide Description ORR is defined as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR); (CR+PR)
Time Frame Month 18
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Duration of Response (DOR)
Hide Description 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
Time Frame Month 18
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description DCR is defined as the proportion of patients with best overall response of CR, PR, or stable disease (SD)
Time Frame Month 18
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Time to Response (TTR)
Hide Description TTR is defined as the time from date of randomization to date of first documented response (CR or PR)
Time Frame Month 18
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Patient Reported Outcomes (PRO)
Hide Description [Not Specified]
Time Frame Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Time to Definitive Deterioration
Hide Description [Not Specified]
Time Frame from the date of randomization to the date of event for disease related symptoms
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Overall Intracranial Response Rate (OIRR)
Hide Description 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.
Time Frame Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Intracranial Disease Control Rate (IDCR)
Hide Description 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.
Time Frame Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Duration of Intracranial Response (DOIR)
Hide Description 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.
Time Frame Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks
Outcome Measure Data Not Reported
Time Frame Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ceritinib Chemotherapy
Hide Arm/Group Description Ceritinib 750 mg Chemotherapy as determined by BIRC.
All-Cause Mortality
Ceritinib Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Ceritinib Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   49/115 (42.61%)   36/113 (31.86%) 
Blood and lymphatic system disorders     
Anaemia  1  0/115 (0.00%)  1/113 (0.88%) 
Febrile Neutropenia  1  0/115 (0.00%)  1/113 (0.88%) 
Cardiac disorders     
Atrial Fibrillation  1  2/115 (1.74%)  1/113 (0.88%) 
Atrial Flutter  1  1/115 (0.87%)  0/113 (0.00%) 
Myocardial Ischaemia  1  1/115 (0.87%)  0/113 (0.00%) 
Pericardial Effusion  1  4/115 (3.48%)  1/113 (0.88%) 
Pericarditis  1  1/115 (0.87%)  0/113 (0.00%) 
Eye disorders     
Lenticular Opacities  1  1/115 (0.87%)  0/113 (0.00%) 
Gastrointestinal disorders     
Abdominal Pain  1  0/115 (0.00%)  1/113 (0.88%) 
Colitis  1  0/115 (0.00%)  1/113 (0.88%) 
Diarrhoea  1  2/115 (1.74%)  0/113 (0.00%) 
Dysphagia  1  1/115 (0.87%)  0/113 (0.00%) 
Faecaloma  1  1/115 (0.87%)  0/113 (0.00%) 
Gastrointestinal Obstruction  1  1/115 (0.87%)  0/113 (0.00%) 
Gastrointestinal Perforation  1  1/115 (0.87%)  0/113 (0.00%) 
Haematemesis  1  0/115 (0.00%)  1/113 (0.88%) 
Nausea  1  6/115 (5.22%)  0/113 (0.00%) 
Vomiting  1  5/115 (4.35%)  0/113 (0.00%) 
General disorders     
Asthenia  1  2/115 (1.74%)  3/113 (2.65%) 
Chest Pain  1  1/115 (0.87%)  0/113 (0.00%) 
Fatigue  1  2/115 (1.74%)  1/113 (0.88%) 
General Physical Health Deterioration  1  5/115 (4.35%)  2/113 (1.77%) 
Malaise  1  1/115 (0.87%)  0/113 (0.00%) 
Non-Cardiac Chest Pain  1  1/115 (0.87%)  0/113 (0.00%) 
Pyrexia  1  4/115 (3.48%)  2/113 (1.77%) 
Hepatobiliary disorders     
Hepatic Failure  1  0/115 (0.00%)  1/113 (0.88%) 
Jaundice  1  1/115 (0.87%)  0/113 (0.00%) 
Infections and infestations     
Bacteraemia  1  0/115 (0.00%)  1/113 (0.88%) 
Bacterial Pyelonephritis  1  0/115 (0.00%)  1/113 (0.88%) 
Biliary Tract Infection  1  1/115 (0.87%)  0/113 (0.00%) 
Lower Respiratory Tract Infection  1  1/115 (0.87%)  0/113 (0.00%) 
Lung Infection  1  0/115 (0.00%)  1/113 (0.88%) 
Neutropenic Sepsis  1  0/115 (0.00%)  2/113 (1.77%) 
Pneumonia  1  5/115 (4.35%)  2/113 (1.77%) 
Respiratory Tract Infection  1  2/115 (1.74%)  0/113 (0.00%) 
Typhoid Fever  1  1/115 (0.87%)  0/113 (0.00%) 
Upper Respiratory Tract Infection  1  0/115 (0.00%)  1/113 (0.88%) 
Urosepsis  1  0/115 (0.00%)  1/113 (0.88%) 
Injury, poisoning and procedural complications     
Hip Fracture  1  0/115 (0.00%)  1/113 (0.88%) 
Investigations     
C-Reactive Protein Increased  1  0/115 (0.00%)  1/113 (0.88%) 
Electrocardiogram Qt Prolonged  1  1/115 (0.87%)  0/113 (0.00%) 
Electrocardiogram T Wave Inversion  1  1/115 (0.87%)  0/113 (0.00%) 
Neutrophil Count Decreased  1  0/115 (0.00%)  1/113 (0.88%) 
Metabolism and nutrition disorders     
Decreased Appetite  1  1/115 (0.87%)  1/113 (0.88%) 
Dehydration  1  2/115 (1.74%)  1/113 (0.88%) 
Hyperglycaemia  1  1/115 (0.87%)  0/113 (0.00%) 
Hypokalaemia  1  1/115 (0.87%)  0/113 (0.00%) 
Hyponatraemia  1  1/115 (0.87%)  0/113 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  0/115 (0.00%)  1/113 (0.88%) 
Back Pain  1  0/115 (0.00%)  2/113 (1.77%) 
Mobility Decreased  1  1/115 (0.87%)  0/113 (0.00%) 
Muscular Weakness  1  2/115 (1.74%)  0/113 (0.00%) 
Pathological Fracture  1  1/115 (0.87%)  0/113 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Metastases To Central Nervous System  1  1/115 (0.87%)  1/113 (0.88%) 
Tumour Flare  1  1/115 (0.87%)  0/113 (0.00%) 
Nervous system disorders     
Aphasia  1  1/115 (0.87%)  0/113 (0.00%) 
Brain Mass  1  1/115 (0.87%)  0/113 (0.00%) 
Brain Oedema  1  0/115 (0.00%)  1/113 (0.88%) 
Cerebrovascular Accident  1  1/115 (0.87%)  0/113 (0.00%) 
Cognitive Disorder  1  1/115 (0.87%)  0/113 (0.00%) 
Coordination Abnormal  1  1/115 (0.87%)  0/113 (0.00%) 
Depressed Level Of Consciousness  1  1/115 (0.87%)  0/113 (0.00%) 
Dizziness  1  0/115 (0.00%)  1/113 (0.88%) 
Epilepsy  1  2/115 (1.74%)  0/113 (0.00%) 
Headache  1  0/115 (0.00%)  1/113 (0.88%) 
Loss Of Consciousness  1  1/115 (0.87%)  0/113 (0.00%) 
Paraesthesia  1  1/115 (0.87%)  0/113 (0.00%) 
Petit Mal Epilepsy  1  1/115 (0.87%)  0/113 (0.00%) 
Seizure  1  1/115 (0.87%)  2/113 (1.77%) 
Syncope  1  0/115 (0.00%)  1/113 (0.88%) 
Visual Field Defect  1  1/115 (0.87%)  0/113 (0.00%) 
Psychiatric disorders     
Confusional State  1  0/115 (0.00%)  1/113 (0.88%) 
Hallucination  1  0/115 (0.00%)  1/113 (0.88%) 
Mental Status Changes  1  0/115 (0.00%)  1/113 (0.88%) 
Renal and urinary disorders     
Urinary Bladder Rupture  1  1/115 (0.87%)  0/113 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  7/115 (6.09%)  5/113 (4.42%) 
Hypoxia  1  1/115 (0.87%)  0/113 (0.00%) 
Interstitial Lung Disease  1  1/115 (0.87%)  1/113 (0.88%) 
Lung Infiltration  1  1/115 (0.87%)  0/113 (0.00%) 
Pleural Effusion  1  5/115 (4.35%)  2/113 (1.77%) 
Pneumonitis  1  0/115 (0.00%)  2/113 (1.77%) 
Respiratory Distress  1  1/115 (0.87%)  0/113 (0.00%) 
Respiratory Failure  1  3/115 (2.61%)  0/113 (0.00%) 
Surgical and medical procedures     
Surgery  1  1/115 (0.87%)  0/113 (0.00%) 
Vascular disorders     
Deep Vein Thrombosis  1  1/115 (0.87%)  0/113 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ceritinib Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   114/115 (99.13%)   111/113 (98.23%) 
Blood and lymphatic system disorders     
Anaemia  1  6/115 (5.22%)  19/113 (16.81%) 
Febrile Neutropenia  1  0/115 (0.00%)  6/113 (5.31%) 
Leukopenia  1  2/115 (1.74%)  9/113 (7.96%) 
Neutropenia  1  4/115 (3.48%)  23/113 (20.35%) 
Gastrointestinal disorders     
Abdominal Pain  1  25/115 (21.74%)  10/113 (8.85%) 
Abdominal Pain Upper  1  18/115 (15.65%)  5/113 (4.42%) 
Constipation  1  22/115 (19.13%)  15/113 (13.27%) 
Diarrhoea  1  81/115 (70.43%)  20/113 (17.70%) 
Nausea  1  73/115 (63.48%)  26/113 (23.01%) 
Stomatitis  1  5/115 (4.35%)  15/113 (13.27%) 
Vomiting  1  58/115 (50.43%)  6/113 (5.31%) 
General disorders     
Asthenia  1  25/115 (21.74%)  19/113 (16.81%) 
Fatigue  1  31/115 (26.96%)  32/113 (28.32%) 
Malaise  1  6/115 (5.22%)  5/113 (4.42%) 
Non-Cardiac Chest Pain  1  14/115 (12.17%)  4/113 (3.54%) 
Oedema Peripheral  1  3/115 (2.61%)  11/113 (9.73%) 
Pyrexia  1  17/115 (14.78%)  16/113 (14.16%) 
Infections and infestations     
Nasopharyngitis  1  12/115 (10.43%)  1/113 (0.88%) 
Investigations     
Alanine Aminotransferase Increased  1  49/115 (42.61%)  10/113 (8.85%) 
Amylase Increased  1  7/115 (6.09%)  3/113 (2.65%) 
Aspartate Aminotransferase Increased  1  42/115 (36.52%)  5/113 (4.42%) 
Blood Alkaline Phosphatase Increased  1  26/115 (22.61%)  1/113 (0.88%) 
Blood Creatinine Increased  1  22/115 (19.13%)  0/113 (0.00%) 
Electrocardiogram Qt Prolonged  1  13/115 (11.30%)  0/113 (0.00%) 
Gamma-Glutamyltransferase Increased  1  26/115 (22.61%)  2/113 (1.77%) 
Neutrophil Count Decreased  1  1/115 (0.87%)  8/113 (7.08%) 
Weight Decreased  1  34/115 (29.57%)  7/113 (6.19%) 
White Blood Cell Count Decreased  1  2/115 (1.74%)  7/113 (6.19%) 
Metabolism and nutrition disorders     
Decreased Appetite  1  48/115 (41.74%)  21/113 (18.58%) 
Hyperglycaemia  1  8/115 (6.96%)  3/113 (2.65%) 
Hypokalaemia  1  10/115 (8.70%)  1/113 (0.88%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  12/115 (10.43%)  12/113 (10.62%) 
Back Pain  1  25/115 (21.74%)  8/113 (7.08%) 
Musculoskeletal Chest Pain  1  9/115 (7.83%)  3/113 (2.65%) 
Musculoskeletal Pain  1  11/115 (9.57%)  4/113 (3.54%) 
Myalgia  1  4/115 (3.48%)  13/113 (11.50%) 
Neck Pain  1  7/115 (6.09%)  2/113 (1.77%) 
Pain In Extremity  1  6/115 (5.22%)  7/113 (6.19%) 
Nervous system disorders     
Dizziness  1  10/115 (8.70%)  6/113 (5.31%) 
Headache  1  22/115 (19.13%)  17/113 (15.04%) 
Neuropathy Peripheral  1  1/115 (0.87%)  9/113 (7.96%) 
Paraesthesia  1  3/115 (2.61%)  6/113 (5.31%) 
Psychiatric disorders     
Insomnia  1  8/115 (6.96%)  11/113 (9.73%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  16/115 (13.91%)  18/113 (15.93%) 
Dyspnoea  1  13/115 (11.30%)  17/113 (15.04%) 
Epistaxis  1  0/115 (0.00%)  6/113 (5.31%) 
Productive Cough  1  5/115 (4.35%)  7/113 (6.19%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  6/115 (5.22%)  24/113 (21.24%) 
Dry Skin  1  6/115 (5.22%)  2/113 (1.77%) 
Pruritus  1  10/115 (8.70%)  6/113 (5.31%) 
Rash  1  13/115 (11.30%)  12/113 (10.62%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Although 116 patients were randomized to the Chemotherapy arm, 3 did not receive study drug and were excluded form the Safety set.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: trialandresults.registries@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01828112    
Other Study ID Numbers: CLDK378A2303
2012-005637-36 ( EudraCT Number )
First Submitted: April 2, 2013
First Posted: April 10, 2013
Results First Submitted: June 24, 2017
Results First Posted: July 27, 2017
Last Update Posted: June 11, 2020