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Ceritinib (LDK378) for Patients Whose Tumors Have Aberrations in ALK or ROS1 (SIGNATURE) (SIGNATURE)

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ClinicalTrials.gov Identifier: NCT02186821
Recruitment Status : Terminated (Study was terminated due to low enrollment)
First Posted : July 10, 2014
Results First Posted : April 8, 2021
Last Update Posted : April 8, 2021
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 Tumors With Aberrations in ALK or ROS1
Intervention Drug: Ceritinib
Enrollment 47
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ceritinib 750 mg
Hide Arm/Group Description Ceritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally, once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days with no breaks between dosing cycles.
Period Title: Overall Study
Started 47
Completed 0
Not Completed 47
Reason Not Completed
Adverse Event             9
Death             2
Disease progression             32
Protocol Violation             1
Physician Decision             1
Study terminated by sponsor             2
Arm/Group Title Ceritinib 750 mg
Hide Arm/Group Description Ceritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally, once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days with no breaks between dosing cycles.
Overall Number of Baseline Participants 47
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 47 participants
<65
27
  57.4%
≥65 - < 75
15
  31.9%
≥75
5
  10.6%
Sex/Gender, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 47 participants
Female Able to bear children
2
   4.3%
Female Premenarche
0
   0.0%
Female Postmenopausal
14
  29.8%
Female Sterile of child bearing age
6
  12.8%
Male
25
  53.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 47 participants
Caucasian
38
  80.9%
Black
2
   4.3%
Asian
3
   6.4%
Native American
1
   2.1%
Other
3
   6.4%
Participants with primary tumor type (sponsor adjudicated)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 47 participants
Ampullary adenocarcinoma
1
   2.1%
Appendix
1
   2.1%
Breast
2
   4.3%
Central nervous system
1
   2.1%
Cervix
1
   2.1%
Colorectal cancer
10
  21.3%
Gastroesophageal junction
1
   2.1%
Head and neck squamous cell carcinoma
1
   2.1%
Liver
1
   2.1%
Lung non-small cell adenocarcinoma
7
  14.9%
Lymphoma
1
   2.1%
Neuroendocrine
1
   2.1%
Ovarian
5
  10.6%
Pancreas
1
   2.1%
Prostate
1
   2.1%
Sarcoma
7
  14.9%
Skin non-melanoma
1
   2.1%
Uterus
2
   4.3%
Uveal Melanoma
2
   4.3%
[1]
Measure Description: Number of participants with primary type of tumor
1.Primary Outcome
Title Percentage of Participants Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) Utilizing RECIST 1.1 at Approximately 16 Weeks
Hide Description Solid tumors were assessed using RECIST 1.1 criteria and included responses of complete response (CR) or partial response (PR) or stable disease (SD). For hematologic tumors, other hematological response criteria applied. CR=disappearance of all target lesions. Pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. PR=at least 30% decrease in sum of diameters of target lesions from baseline sum diameters. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. Progressive disease (PD)=at least a 20% increase in sum of diameter of measured target lesions from smallest sum of diameter of all target lesions recorded at or after baseline (sum must also demonstrate an absolute increase of at least 5mm). One or more new lesions was considered PD. Overall response rate (ORR) = (CR + PR). Clinical benefit rate = (CR + PR + SD)
Time Frame Baseline up to approximately 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ORR and CBR was reported for all patients and for a subgroup of patients with colorectal cancer
Arm/Group Title Ceritinib 750 mg
Hide Arm/Group Description:
Ceritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally, once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days with no breaks between dosing cycles.
Overall Number of Participants Analyzed 47
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of paarticipants
ORR (CR + PR) for all patients Number Analyzed 47 participants
6.4
(1.3 to 17.5)
CBR (CR + PR + SD) for all patients Number Analyzed 47 participants
19.1
(9.1 to 33.3)
ORR (CR + PR) for colorectal cancer patients Number Analyzed 10 participants
0.0
(0.0 to 30.8)
CBR (CR + PR + SD) for colorectal cancer Number Analyzed 10 participants
10.0
(0.3 to 44.5)
2.Primary Outcome
Title Number of Participants With Tumor Responses Utilizing RECIST 1.1 at Approximately 16 Weeks
Hide Description For patients with solid tumors the assessment criteria was RECIST 1.1 and included responses of complete response (CR) or partial response (PR) or stable disease (SD). For hematologic tumors, other hematological response criteria applied. CR=disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. PR=at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. Progressive disease (PD)=at least a 20% increase in sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline (sum must also demonstrate an absolute increase of at least 5mm). One or more new lesions was also considered progression.
Time Frame Baseline up to approximately 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
tumor response was reported for all patients and for a subgroup of patients with colorectal cancer
Arm/Group Title Ceritinib 750 mg
Hide Arm/Group Description:
Ceritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally, once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days with no breaks between dosing cycles.
Overall Number of Participants Analyzed 47
Measure Type: Count of Participants
Unit of Measure: Participants
Complete response - all patients Number Analyzed 47 participants
0
   0.0%
Partial response - all patients Number Analyzed 47 participants
3
   6.4%
Stable disease- all patients Number Analyzed 47 participants
6
  12.8%
Progressive disease - all patients Number Analyzed 47 participants
32
  68.1%
Non-evaluable - all patients Number Analyzed 47 participants
6
  12.8%
Stable disease - Colorectal cancer patients Number Analyzed 10 participants
1
  10.0%
PD - Colorectal cancer patients Number Analyzed 10 participants
8
  80.0%
Non-evaluable - Colorectal cancer patients Number Analyzed 10 participants
1
  10.0%
3.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description Progression-free survival (PFS) was the time from the date of start of study drug to the date of event defined as the first documented progression or death due to any cause within 30 days of the last dose. If a patient has not had an event, progression-free survival was censored at the date of last adequate tumor assessment.
Time Frame Baseline up to approximately 27 months
Hide Outcome Measure Data
Hide Analysis Population Description
reported for all patients and for a subgroup of patients with colorectal cancer
Arm/Group Title Ceritinib 750 mg
Hide Arm/Group Description:
Ceritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally, once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days with no breaks between dosing cycles.
Overall Number of Participants Analyzed 47
Median (95% Confidence Interval)
Unit of Measure: months
All patients Number Analyzed 36 participants
1.8
(1.5 to 1.9)
Colorectal cancer patients Number Analyzed 9 participants
1.8
(1.0 to 1.9)
4.Secondary Outcome
Title Percentage of Participants With Progression-Free Survival (PFS) - Kaplan-Meier Estimates
Hide Description Progression-free survival (PFS) was the time from the date of start of study drug to the date of event defined as the first documented progression or death due to any cause within 30 days of the last dose. If a patient has not had an event, progression-free survival was censored at the date of last adequate tumor assessment.
Time Frame Basleline up to approximately 27 months
Hide Outcome Measure Data
Hide Analysis Population Description
reported for all patients and for a subgroup of patients with colorectal cancer
Arm/Group Title Ceritinib 750 mg
Hide Arm/Group Description:
Ceritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally, once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days with no breaks between dosing cycles.
Overall Number of Participants Analyzed 47
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
1 Month Number Analyzed 47 participants
81.0
(65.5 to 90.0)
2 Month Number Analyzed 47 participants
34.8
(20.8 to 49.2)
3 Month Number Analyzed 47 participants
34.8
(20.8 to 49.2)
4 Month Number Analyzed 47 participants
24.1
(12.3 to 38.2)
5 Month Number Analyzed 47 participants
21.4
(10.3 to 35.2)
6 Month Number Analyzed 47 participants
15.3
(6.0 to 28.6)
9 Month Number Analyzed 47 participants
11.5
(3.5 to 24.8)
12 Month Number Analyzed 47 participants
7.7
(1.6 to 20.5)
18 Month Number Analyzed 47 participants
7.7
(1.6 to 20.5)
24 Month Number Analyzed 47 participants
7.7
(1.6 to 20.5)
30 Month Number Analyzed 47 participants
7.7
(1.6 to 20.5)
1 Month Colorectal cancer patients Number Analyzed 10 participants
90.0
(47.3 to 98.5)
2 Month Colorectal cancer patients Number Analyzed 10 participants
12.5
(0.7 to 41.8)
3 Month Colorectal cancer patients Number Analyzed 10 participants
12.5
(0.7 to 41.8)
4 Mongth Colorectal cancer patients Number Analyzed 10 participants
12.5
(0.7 to 41.8)
5 Month Colorectal cancer patients Number Analyzed 10 participants
12.5
(0.7 to 41.8)
6 Month Colorectal cancer patients Number Analyzed 10 participants
12.5
(0.7 to 41.8)
9 Month Colorectal cancer patients Number Analyzed 10 participants
12.5
(0.7 to 41.8)
5.Secondary Outcome
Title Overall Survival (OS) - Number of Participant Deaths
Hide Description Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause
Time Frame Baseline up to approximately 27 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ceritinib 750 mg
Hide Arm/Group Description:
Ceritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally, once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days with no breaks between dosing cycles.
Overall Number of Participants Analyzed 47
Measure Type: Count of Participants
Unit of Measure: Participants
Deaths due to study indication
14
  29.8%
Deaths due to study indication while on treatment
5
  10.6%
6.Secondary Outcome
Title Duration of Response (DOR)
Hide Description Duration of response (DOR) is defined as time from the first documented response (CR or PR) to the date first documented disease progression or relapse or death due to any cause
Time Frame baseline up to approximately 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
only 2 patients met criteria for duration of response
Arm/Group Title Ceritinib 750 mg
Hide Arm/Group Description:
Ceritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally, once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days with no breaks between dosing cycles.
Overall Number of Participants Analyzed 47
Measure Type: Number
Unit of Measure: days
One Patient with PR Number Analyzed 1 participants
132
Second Patient with PR Number Analyzed 1 participants
113
7.Post-Hoc Outcome
Title All Collected Deaths
Hide Description On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 27 months (treatment duration ranged from 0.2 to 25.9 months). Deaths post treatment survival follow up were collected after the on treatment period, up to approximately 39 months.
Time Frame approx. 26 months, approx. 39 months
Hide Outcome Measure Data
Hide Analysis Population Description
Clinical Database Population: All treated patients
Arm/Group Title Ceritinib 750 mg
Hide Arm/Group Description:
Ceritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally, once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days with no breaks between dosing cycles.
Overall Number of Participants Analyzed 47
Measure Type: Number
Unit of Measure: Participants
Total deaths 14
Deaths on treatment 5
Time Frame Adverse events were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 27 months (treatment duration ranged from 0.2 to 26.9 months).
Adverse Event Reporting Description AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
 
Arm/Group Title Ceritinib 750 mg
Hide Arm/Group Description Ceritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally, once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days with no breaks between dosing cycles.
All-Cause Mortality
Ceritinib 750 mg
Affected / at Risk (%)
Total   5/47 (10.64%) 
Hide Serious Adverse Events
Ceritinib 750 mg
Affected / at Risk (%)
Total   16/47 (34.04%) 
Blood and lymphatic system disorders   
Lymphadenopathy  1  1/47 (2.13%) 
Gastrointestinal disorders   
Abdominal distension  1  1/47 (2.13%) 
Abdominal pain  1  2/47 (4.26%) 
Diarrhoea  1  3/47 (6.38%) 
Ileus  1  1/47 (2.13%) 
Nausea  1  2/47 (4.26%) 
Small intestinal obstruction  1  1/47 (2.13%) 
General disorders   
Asthenia  1  1/47 (2.13%) 
Fatigue  1  1/47 (2.13%) 
Malaise  1  1/47 (2.13%) 
Pyrexia  1  1/47 (2.13%) 
Hepatobiliary disorders   
Hyperbilirubinaemia  1  2/47 (4.26%) 
Jaundice cholestatic  1  1/47 (2.13%) 
Infections and infestations   
Clostridium difficile infection  1  1/47 (2.13%) 
Pneumonia  1  3/47 (6.38%) 
Injury, poisoning and procedural complications   
Fall  1  1/47 (2.13%) 
Subarachnoid haemorrhage  1  1/47 (2.13%) 
Investigations   
Alanine aminotransferase increased  1  2/47 (4.26%) 
Aspartate aminotransferase increased  1  2/47 (4.26%) 
Blood alkaline phosphatase increased  1  1/47 (2.13%) 
Blood bilirubin increased  1  1/47 (2.13%) 
Gamma-glutamyltransferase increased  1  1/47 (2.13%) 
Metabolism and nutrition disorders   
Dehydration  1  1/47 (2.13%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  1/47 (2.13%) 
Muscular weakness  1  1/47 (2.13%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Tongue neoplasm  1  1/47 (2.13%) 
Nervous system disorders   
Aphasia  1  1/47 (2.13%) 
Presyncope  1  1/47 (2.13%) 
Transient ischaemic attack  1  1/47 (2.13%) 
Reproductive system and breast disorders   
Vaginal haemorrhage  1  1/47 (2.13%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  3/47 (6.38%) 
Hypoxia  1  1/47 (2.13%) 
Respiratory failure  1  1/47 (2.13%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ceritinib 750 mg
Affected / at Risk (%)
Total   46/47 (97.87%) 
Blood and lymphatic system disorders   
Anaemia  1  7/47 (14.89%) 
Gastrointestinal disorders   
Abdominal distension  1  3/47 (6.38%) 
Abdominal pain  1  12/47 (25.53%) 
Constipation  1  9/47 (19.15%) 
Diarrhoea  1  36/47 (76.60%) 
Dyspepsia  1  3/47 (6.38%) 
Nausea  1  33/47 (70.21%) 
Vomiting  1  24/47 (51.06%) 
General disorders   
Fatigue  1  24/47 (51.06%) 
Oedema peripheral  1  3/47 (6.38%) 
Hepatobiliary disorders   
Hyperbilirubinaemia  1  3/47 (6.38%) 
Infections and infestations   
Oral candidiasis  1  3/47 (6.38%) 
Urinary tract infection  1  4/47 (8.51%) 
Investigations   
Alanine aminotransferase increased  1  15/47 (31.91%) 
Aspartate aminotransferase increased  1  19/47 (40.43%) 
Blood alkaline phosphatase increased  1  13/47 (27.66%) 
Blood creatine phosphokinase increased  1  3/47 (6.38%) 
Blood creatinine increased  1  14/47 (29.79%) 
Electrocardiogram QT prolonged  1  4/47 (8.51%) 
Gamma-glutamyltransferase increased  1  12/47 (25.53%) 
Weight decreased  1  7/47 (14.89%) 
Metabolism and nutrition disorders   
Decreased appetite  1  17/47 (36.17%) 
Dehydration  1  6/47 (12.77%) 
Hyperglycaemia  1  4/47 (8.51%) 
Hyperuricaemia  1  5/47 (10.64%) 
Hypokalaemia  1  4/47 (8.51%) 
Hypomagnesaemia  1  6/47 (12.77%) 
Hyponatraemia  1  5/47 (10.64%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  4/47 (8.51%) 
Muscle spasms  1  3/47 (6.38%) 
Musculoskeletal chest pain  1  3/47 (6.38%) 
Pain in extremity  1  3/47 (6.38%) 
Nervous system disorders   
Headache  1  4/47 (8.51%) 
Renal and urinary disorders   
Chromaturia  1  3/47 (6.38%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  9/47 (19.15%) 
Dyspnoea  1  7/47 (14.89%) 
Pleural effusion  1  3/47 (6.38%) 
Skin and subcutaneous tissue disorders   
Pruritus  1  3/47 (6.38%) 
Rash  1  6/47 (12.77%) 
Vascular disorders   
Hypotension  1  3/47 (6.38%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
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 the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 1-888-669-6682
EMail: Novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02186821    
Other Study ID Numbers: CLDK378AUS23
First Submitted: July 3, 2014
First Posted: July 10, 2014
Results First Submitted: December 11, 2018
Results First Posted: April 8, 2021
Last Update Posted: April 8, 2021