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

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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 )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non-Small Cell Lung Cancer
Intervention Drug: LDK378
Enrollment 140
Recruitment Details  
Pre-assignment Details Approximately 137 patients were planned to be enrolled. A total of 140 patients were enrolled and treated with ceritinib.
Arm/Group Title LDK378 750mg
Hide Arm/Group Description Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.
Period Title: Overall Study
Started 140
Entered Post-treatment Efficacy f/u 7
Entered Survival Follow up 98
Discontinued From Study 35
Completed 0
Not Completed 140
Reason Not Completed
Rollover patients             16
Adverse Event             12
Progressive disease             69
Physician Decision             14
Subject/guardian decision             20
Lost to Follow-up             1
Death             8
Arm/Group Title LDK378 750mg
Hide Arm/Group Description Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.
Overall Number of Baseline Participants 140
Hide Baseline Analysis Population Description
Full Analysis Set (FAS) consisted of all patients who received at least one dose of ceritinib.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 140 participants
51.2  (11.62)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 140 participants
Female
70
  50.0%
Male
70
  50.0%
1.Primary Outcome
Title Overall Response Rate (ORR) to LDK378 Per Investigator Assessment
Hide Description 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.
Time Frame 6 cycles of 28 days up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) consisted of all patients who received at least one dose of ceritinib.
Arm/Group Title LDK378 750mg
Hide Arm/Group Description:
Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.
Overall Number of Participants Analyzed 140
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
40.7
(32.5 to 49.3)
2.Secondary Outcome
Title ORR Per Blinded Independent Review Committee (BIRC) Assessment
Hide Description 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.
Time Frame 6 cycles of 28 days up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib.
Arm/Group Title LDK378 750mg
Hide Arm/Group Description:
Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.
Overall Number of Participants Analyzed 140
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
35.7
(27.8 to 44.2)
3.Secondary Outcome
Title Duration of Response (DOR) by Investigator
Hide Description 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.
Time Frame 6 cycles of 28 days up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) consisted of all patients who received at least one dose of ceritinib. Only patients with confirmed complete response/partial response (CR/PR) per Investigator were included in this analysis.
Arm/Group Title LDK378 750mg
Hide Arm/Group Description:
Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.
Overall Number of Participants Analyzed 57
Median (95% Confidence Interval)
Unit of Measure: Months
10.6
(7.4 to 14.7)
4.Secondary Outcome
Title Duration of Response (DOR) by BIRC
Hide Description 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.
Time Frame 6 cycles of 28 days up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) consisted of all patients who received at least one dose of ceritinib. Only patients with confirmed complete response/partial response (CR/PR) per BIRC were included in this analysis.
Arm/Group Title LDK378 750mg
Hide Arm/Group Description:
Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.
Overall Number of Participants Analyzed 50
Median (95% Confidence Interval)
Unit of Measure: Months
12.9
(9.3 to 18.4)
5.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description 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 Frame 6 cycles of 28 days up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) consisted of all patients who received at least one dose of ceritinib.
Arm/Group Title LDK378 750mg
Hide Arm/Group Description:
Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.
Overall Number of Participants Analyzed 140
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
DCR per Investigator
76.4
(68.5 to 83.2)
DCR per BIRC
80.0
(72.4 to 86.3)
6.Secondary Outcome
Title Time to Response (TTR) Per Investigator
Hide Description TTR is the time from date of start of treatment to the first CR or PR observed which were confirmed afterwards.
Time Frame 6 cycles of 28 days up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib. Only patients with confirmed complete response/partial response (CR/PR) were included in this analysis.
Arm/Group Title LDK378 750mg
Hide Arm/Group Description:
Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.
Overall Number of Participants Analyzed 57
Mean (Standard Deviation)
Unit of Measure: Months
3.0  (3.54)
7.Secondary Outcome
Title Time to Response (TTR) Per BIRC
Hide Description TTR is the time from date of start of treatment to the first CR or PR observed which are confirmed afterwards.
Time Frame 6 cycles of 28 days up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib. Only patients with confirmed complete response/partial response (CR/PR) were included in this analysis.
Arm/Group Title LDK378 750mg
Hide Arm/Group Description:
Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.
Overall Number of Participants Analyzed 50
Mean (Standard Deviation)
Unit of Measure: Months
2.2  (1.44)
8.Secondary Outcome
Title Progression-free Survival (PFS) Per Investigator
Hide Description 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.
Time Frame 6 cycles of 28 days up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib.
Arm/Group Title LDK378 750mg
Hide Arm/Group Description:
Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.
Overall Number of Participants Analyzed 140
Median (95% Confidence Interval)
Unit of Measure: months
5.8
(5.4 to 7.6)
9.Secondary Outcome
Title Progression-free Survival (PFS) Per BIRC
Hide Description 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.
Time Frame 6 cycles of 28 days up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib.
Arm/Group Title LDK378 750mg
Hide Arm/Group Description:
Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.
Overall Number of Participants Analyzed 140
Median (95% Confidence Interval)
Unit of Measure: months
7.4
(5.6 to 10.9)
10.Secondary Outcome
Title Overall Intracranial Response Rate (OIRR) Per Investigator
Hide Description OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.
Time Frame 6 cycles of 28 days up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib. Only patients with measurable disease in brain at baseline selected by Investigator were included in this analysis.
Arm/Group Title LDK378 750mg
Hide Arm/Group Description:
Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.
Overall Number of Participants Analyzed 20
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
45.0
(23.1 to 68.5)
11.Secondary Outcome
Title Overall Intracranial Response Rate (OIRR) Per BIRC
Hide Description OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.
Time Frame 6 cycles of 28 days up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib. Only patients with measurable disease in brain at baseline selected by BIRC were included in this analysis.
Arm/Group Title LDK378 750mg
Hide Arm/Group Description:
Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.
Overall Number of Participants Analyzed 28
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
35.7
(18.6 to 55.9)
12.Secondary Outcome
Title Overall Survival (OS)
Hide Description 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.
Time Frame 6 cycles of 28 days up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) consisted of all patients who received at least one dose of ceritinib.
Arm/Group Title LDK378 750mg
Hide Arm/Group Description:
Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.
Overall Number of Participants Analyzed 140
Median (95% Confidence Interval)
Unit of Measure: Months
15.6
(13.6 to 24.2)
Time Frame Timeframe for AE
Adverse Event Reporting Description AE additional description
 
Arm/Group Title LDK378 750 mg
Hide Arm/Group Description Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.
All-Cause Mortality
LDK378 750 mg
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
LDK378 750 mg
Affected / at Risk (%)
Total   67/140 (47.86%) 
Blood and lymphatic system disorders   
ANAEMIA † 1  1/140 (0.71%) 
FEBRILE NEUTROPENIA † 1  2/140 (1.43%) 
THROMBOCYTOPENIA † 1  1/140 (0.71%) 
Cardiac disorders   
CORONARY ARTERY DISEASE † 1  1/140 (0.71%) 
PERICARDIAL EFFUSION † 1  2/140 (1.43%) 
PERICARDITIS † 1  2/140 (1.43%) 
Gastrointestinal disorders   
ABDOMINAL PAIN † 1  3/140 (2.14%) 
ASCITES † 1  1/140 (0.71%) 
CONSTIPATION † 1  1/140 (0.71%) 
DYSPHAGIA † 1  1/140 (0.71%) 
FAECALOMA † 1  1/140 (0.71%) 
GASTROINTESTINAL DISORDER † 1  1/140 (0.71%) 
GASTROINTESTINAL TOXICITY † 1  1/140 (0.71%) 
INTESTINAL PERFORATION † 1  1/140 (0.71%) 
NAUSEA † 1  3/140 (2.14%) 
PANCREATITIS † 1  2/140 (1.43%) 
RETROPERITONEAL FIBROSIS † 1  1/140 (0.71%) 
VOMITING † 1  4/140 (2.86%) 
General disorders   
ASTHENIA † 1  3/140 (2.14%) 
DISEASE PROGRESSION † 1  1/140 (0.71%) 
GENERAL PHYSICAL HEALTH DETERIORATION † 1  2/140 (1.43%) 
MALAISE † 1  3/140 (2.14%) 
NON-CARDIAC CHEST PAIN † 1  3/140 (2.14%) 
PAIN † 1  2/140 (1.43%) 
PYREXIA † 1  8/140 (5.71%) 
Hepatobiliary disorders   
HEPATIC FUNCTION ABNORMAL † 1  1/140 (0.71%) 
HEPATOCELLULAR INJURY † 1  1/140 (0.71%) 
Infections and infestations   
EMPYEMA † 1  1/140 (0.71%) 
ENTERITIS INFECTIOUS † 1  1/140 (0.71%) 
LUNG INFECTION † 1  1/140 (0.71%) 
MENINGITIS † 1  1/140 (0.71%) 
PLEURAL INFECTION † 1  1/140 (0.71%) 
PNEUMONIA † 1  6/140 (4.29%) 
RESPIRATORY TRACT INFECTION † 1  1/140 (0.71%) 
SEPTIC SHOCK † 1  1/140 (0.71%) 
URINARY TRACT INFECTION † 1  1/140 (0.71%) 
VIRAL PERICARDITIS † 1  1/140 (0.71%) 
Injury, poisoning and procedural complications   
HUMERUS FRACTURE † 1  1/140 (0.71%) 
PUBIS FRACTURE † 1  1/140 (0.71%) 
SPINAL COMPRESSION FRACTURE † 1  1/140 (0.71%) 
Investigations   
ALANINE AMINOTRANSFERASE INCREASED † 1  1/140 (0.71%) 
ASPARTATE AMINOTRANSFERASE INCREASED † 1  1/140 (0.71%) 
BLOOD CALCIUM INCREASED † 1  1/140 (0.71%) 
BLOOD CREATINE PHOSPHOKINASE INCREASED † 1  1/140 (0.71%) 
BLOOD CREATININE INCREASED † 1  2/140 (1.43%) 
WEIGHT DECREASED † 1  2/140 (1.43%) 
Metabolism and nutrition disorders   
DECREASED APPETITE † 1  2/140 (1.43%) 
DEHYDRATION † 1  4/140 (2.86%) 
DIABETES MELLITUS † 1  1/140 (0.71%) 
HYPERGLYCAEMIA † 1  1/140 (0.71%) 
Musculoskeletal and connective tissue disorders   
BACK PAIN † 1  1/140 (0.71%) 
BONE PAIN † 1  1/140 (0.71%) 
NECK PAIN † 1  1/140 (0.71%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
COLON CANCER † 1  1/140 (0.71%) 
METASTASES TO LIVER † 1  1/140 (0.71%) 
METASTASES TO LUNG † 1  1/140 (0.71%) 
METASTASES TO MENINGES † 1  2/140 (1.43%) 
Nervous system disorders   
ALTERED STATE OF CONSCIOUSNESS † 1  1/140 (0.71%) 
APHASIA † 1  2/140 (1.43%) 
BRAIN OEDEMA † 1  2/140 (1.43%) 
CEREBROVASCULAR ACCIDENT † 1  1/140 (0.71%) 
DYSARTHRIA † 1  1/140 (0.71%) 
ENCEPHALOPATHY † 1  1/140 (0.71%) 
HEADACHE † 1  1/140 (0.71%) 
HEPATIC ENCEPHALOPATHY † 1  1/140 (0.71%) 
HYPERAESTHESIA † 1  1/140 (0.71%) 
LETHARGY † 1  1/140 (0.71%) 
MOTOR DYSFUNCTION † 1  1/140 (0.71%) 
PARAESTHESIA † 1  1/140 (0.71%) 
PARAPARESIS † 1  1/140 (0.71%) 
SEIZURE † 1  4/140 (2.86%) 
SENSORY LOSS † 1  1/140 (0.71%) 
Psychiatric disorders   
CONFUSIONAL STATE † 1  2/140 (1.43%) 
Renal and urinary disorders   
HYDRONEPHROSIS † 1  1/140 (0.71%) 
POLLAKIURIA † 1  1/140 (0.71%) 
RENAL FAILURE † 1  1/140 (0.71%) 
RENAL IMPAIRMENT † 1  1/140 (0.71%) 
Respiratory, thoracic and mediastinal disorders   
COUGH † 1  1/140 (0.71%) 
DYSPNOEA † 1  7/140 (5.00%) 
LUNG DISORDER † 1  1/140 (0.71%) 
PLEURAL EFFUSION † 1  3/140 (2.14%) 
PLEURISY † 1  2/140 (1.43%) 
PNEUMONITIS † 1  3/140 (2.14%) 
PULMONARY EMBOLISM † 1  2/140 (1.43%) 
PULMONARY HYPERTENSION † 1  1/140 (0.71%) 
RESPIRATORY FAILURE † 1  3/140 (2.14%) 
†
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%
LDK378 750 mg
Affected / at Risk (%)
Total   139/140 (99.29%) 
Blood and lymphatic system disorders   
ANAEMIA † 1  25/140 (17.86%) 
Gastrointestinal disorders   
ABDOMINAL PAIN † 1  45/140 (32.14%) 
ABDOMINAL PAIN UPPER † 1  16/140 (11.43%) 
CONSTIPATION † 1  42/140 (30.00%) 
DIARRHOEA † 1  115/140 (82.14%) 
NAUSEA † 1  115/140 (82.14%) 
STOMATITIS † 1  11/140 (7.86%) 
VOMITING † 1  92/140 (65.71%) 
General disorders   
ASTHENIA † 1  25/140 (17.86%) 
FATIGUE † 1  54/140 (38.57%) 
NON-CARDIAC CHEST PAIN † 1  25/140 (17.86%) 
OEDEMA PERIPHERAL † 1  19/140 (13.57%) 
PYREXIA † 1  28/140 (20.00%) 
Infections and infestations   
NASOPHARYNGITIS † 1  9/140 (6.43%) 
PNEUMONIA † 1  9/140 (6.43%) 
UPPER RESPIRATORY TRACT INFECTION † 1  18/140 (12.86%) 
Investigations   
ALANINE AMINOTRANSFERASE INCREASED † 1  65/140 (46.43%) 
ASPARTATE AMINOTRANSFERASE INCREASED † 1  55/140 (39.29%) 
BLOOD ALKALINE PHOSPHATASE INCREASED † 1  23/140 (16.43%) 
BLOOD CREATININE INCREASED † 1  27/140 (19.29%) 
ELECTROCARDIOGRAM QT PROLONGED † 1  12/140 (8.57%) 
GAMMA-GLUTAMYLTRANSFERASE INCREASED † 1  26/140 (18.57%) 
WEIGHT DECREASED † 1  48/140 (34.29%) 
Metabolism and nutrition disorders   
DECREASED APPETITE † 1  59/140 (42.14%) 
HYPOKALAEMIA † 1  8/140 (5.71%) 
HYPOPHOSPHATAEMIA † 1  9/140 (6.43%) 
Musculoskeletal and connective tissue disorders   
ARTHRALGIA † 1  16/140 (11.43%) 
BACK PAIN † 1  28/140 (20.00%) 
MUSCULOSKELETAL CHEST PAIN † 1  9/140 (6.43%) 
MUSCULOSKELETAL PAIN † 1  14/140 (10.00%) 
MYALGIA † 1  10/140 (7.14%) 
NECK PAIN † 1  11/140 (7.86%) 
PAIN IN EXTREMITY † 1  14/140 (10.00%) 
Nervous system disorders   
DIZZINESS † 1  15/140 (10.71%) 
DYSGEUSIA † 1  12/140 (8.57%) 
HEADACHE † 1  31/140 (22.14%) 
PARAESTHESIA † 1  8/140 (5.71%) 
Psychiatric disorders   
ANXIETY † 1  11/140 (7.86%) 
INSOMNIA † 1  18/140 (12.86%) 
Respiratory, thoracic and mediastinal disorders   
COUGH † 1  33/140 (23.57%) 
DYSPNOEA † 1  29/140 (20.71%) 
HAEMOPTYSIS † 1  10/140 (7.14%) 
Skin and subcutaneous tissue disorders   
ALOPECIA † 1  9/140 (6.43%) 
DRY SKIN † 1  10/140 (7.14%) 
PRURITUS † 1  8/140 (5.71%) 
RASH † 1  24/140 (17.14%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.1)
[Not Specified]
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
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01685060    
Other Study ID Numbers: CLDK378A2201
2012-003432-24 ( EudraCT Number )
First Submitted: September 4, 2012
First Posted: September 13, 2012
Results First Submitted: March 27, 2017
Results First Posted: May 8, 2017
Last Update Posted: June 19, 2017