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Efficacy and Safety of Dovitinib in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib

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ClinicalTrials.gov Identifier: NCT01478373
Recruitment Status : Completed
First Posted : November 23, 2011
Results First Posted : August 10, 2015
Last Update Posted : April 27, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Gastrointestinal Stromal Tumors
Intervention Drug: Dovitinib (TKI258)
Enrollment 39
Recruitment Details  
Pre-assignment Details 39 Patients enrolled. One patient had a protocol deviation which excluded him from the Full Analysis Set.
Arm/Group Title Dovitinib
Hide Arm/Group Description Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Period Title: Treatment Phase
Started 39
Completed 38
Not Completed 1
Reason Not Completed
Protocol Violation             1
Period Title: Survival Phase
Started 38
Completed 0
Not Completed 38
Reason Not Completed
Adverse Event             8
Protocol Violation             1
crossover to another study             2
Progressive Disease             27
Arm/Group Title Dovitinib
Hide Arm/Group Description Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Baseline Participants 38
Hide Baseline Analysis Population Description
Full Analysis Set - All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 38 participants
59.2  (10.14)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants
Female
16
  42.1%
Male
22
  57.9%
1.Primary Outcome
Title Antitumor Activity of Dovitinib in Terms of Disease Control Rate (DCR): Complete Response+Partial Response +Stable Disease
Hide Description DCR is defined as the proportion of patients with a best overall response of Complete Responses (CR), Partial Response (PR) and Stable Disease (SD) at 12 weeks according to RECIST (version 1.1). Complete Response (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;Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the 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. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.
Time Frame 12 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.
Arm/Group Title Dovitinib
Hide Arm/Group Description:
Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 38
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of Participants
52.6
(38.2 to 66.7)
2.Secondary Outcome
Title Progression-free Survival (PFS) of Patients Treated With Dovitinib
Hide Description The PFS duration: time from entry into the study to the date of the first documented progression (assessed using conventional RECIST (version 1.1) or death due to any cause. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.
Arm/Group Title Dovitinib
Hide Arm/Group Description:
Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 38
Median (90% Confidence Interval)
Unit of Measure: Days
141
(86.0 to 225.0)
3.Secondary Outcome
Title Time to Treatment Failure (TTF)of Patients Treated With Dovitinib
Hide Description TTF: the date of entry into the study to the earliest date of the first objective tumor progression, date of death due to any cause, or date of discontinuation due to reasons other than 'Protocol deviation' or 'Administrative problems'.
Time Frame 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.
Arm/Group Title Dovitinib
Hide Arm/Group Description:
Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 38
Median (95% Confidence Interval)
Unit of Measure: Days
122.0
(81.0 to 223.0)
4.Secondary Outcome
Title Duration of Response or Stable Disease (SD)
Hide Description Duration of response or SD: time from date of entry into study to earliest date of first objective tumor progression or death. DCR is defined as proportion of patients with best overall response of CR, PR and SD at 12 weeks according to RECIST (version 1.1). CR: Disappearance of all non-nodal target lesions. 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 sum of diameter of all target lesions, taking as reference the baseline sum of diameters. PD: At least a 20% increase in the 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. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.
Time Frame 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.
Arm/Group Title Dovitinib
Hide Arm/Group Description:
Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 38
Mean (Standard Deviation)
Unit of Measure: Days
193.2  (117.78)
5.Secondary Outcome
Title Time to Tumor Progression (TTP)of Patients Treated With Dovitinib
Hide Description TTP: time from the date of entry into the study to first documentation of tumor progression or death due to the underlying cancer. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.
Arm/Group Title Dovitinib
Hide Arm/Group Description:
Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 38
Median (95% Confidence Interval)
Unit of Measure: Days
141.0
(85.0 to 229.0)
6.Secondary Outcome
Title Overall Response Rate (ORR) of Patients Treated With Dovitinib
Hide Description Outcome Measure Description: ORR: proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST (version 1.1). Complete Response (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;Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the 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. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.
Time Frame Baseline, 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.
Arm/Group Title Dovitinib
Hide Arm/Group Description:
Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 38
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of Participants
2.6
(0.1 to 11.9)
7.Secondary Outcome
Title Overall Survival (OS) of Patients Treated With Dovitinib
Hide Description Outcome Measure Description: OS: time from the date of entry into the study to the date of death due to any cause. A patient who has not died by the date of the analysis cut-off would have the OS censored at the time of the last contact before the cut-off date.
Time Frame 21 months (9 months of estimated treatment plus 12 months of survival follow up)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.
Arm/Group Title Dovitinib
Hide Arm/Group Description:
Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 38
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
[1]
The median survival had not been reached
8.Secondary Outcome
Title DCR (CR+PR+SD) at the End of Treatment
Hide Description DCR is defined as the proportion of patients with a best overall response of CR, PR and SD at the end of dovitinib treatment according to RECIST (version 1.1). Complete Response (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;Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the 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. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.
Time Frame Up to 9 months of estimated treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.
Arm/Group Title Dovitinib
Hide Arm/Group Description:
Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 38
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of Participants
52.6
(38.2 to 66.7)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Dovitinib
Hide Arm/Group Description Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
All-Cause Mortality
Dovitinib
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Dovitinib
Affected / at Risk (%)
Total   16/39 (41.03%) 
Blood and lymphatic system disorders   
Anaemia  1  1/39 (2.56%) 
Leukopenia  1  1/39 (2.56%) 
Pancytopenia  1  1/39 (2.56%) 
Cardiac disorders   
Cardiac arrest  1  1/39 (2.56%) 
Tachycardia  1  1/39 (2.56%) 
Gastrointestinal disorders   
Abdominal pain  1  1/39 (2.56%) 
Abdominal pain upper  1  1/39 (2.56%) 
Ascites  1  1/39 (2.56%) 
Diarrhoea  1  2/39 (5.13%) 
Nausea  1  1/39 (2.56%) 
Peritoneal haemorrhage  1  1/39 (2.56%) 
Vomiting  1  3/39 (7.69%) 
General disorders   
Asthenia  1  1/39 (2.56%) 
Fatigue  1  4/39 (10.26%) 
General physical health deterioration  1  1/39 (2.56%) 
Inflammation  1  1/39 (2.56%) 
Localised oedema  1  1/39 (2.56%) 
Mucosal dryness  1  1/39 (2.56%) 
Oedema peripheral  1  1/39 (2.56%) 
Systemic inflammatory response syndrome  1  1/39 (2.56%) 
Hepatobiliary disorders   
Cholestasis  1  1/39 (2.56%) 
Infections and infestations   
H1N1 influenza  1  1/39 (2.56%) 
Tracheobronchitis  1  1/39 (2.56%) 
Investigations   
Red blood cell count decreased  1  1/39 (2.56%) 
Weight decreased  1  1/39 (2.56%) 
Metabolism and nutrition disorders   
Decreased appetite  1  2/39 (5.13%) 
Dehydration  1  1/39 (2.56%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Malignant melanoma  1  1/39 (2.56%) 
Prostate cancer  1  1/39 (2.56%) 
Nervous system disorders   
Neuropathy peripheral  1  1/39 (2.56%) 
Paraesthesia  1  1/39 (2.56%) 
Psychiatric disorders   
Mania  1  1/39 (2.56%) 
Respiratory, thoracic and mediastinal disorders   
Chronic obstructive pulmonary disease  1  1/39 (2.56%) 
Dyspnoea  1  1/39 (2.56%) 
Hiccups  1  1/39 (2.56%) 
Lung disorder  1  1/39 (2.56%) 
Pulmonary embolism  1  2/39 (5.13%) 
Skin and subcutaneous tissue disorders   
Toxic skin eruption  1  1/39 (2.56%) 
Vascular disorders   
Aortic thrombosis  1  1/39 (2.56%) 
Phlebitis  1  1/39 (2.56%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dovitinib
Affected / at Risk (%)
Total   36/39 (92.31%) 
Blood and lymphatic system disorders   
Anaemia  1  6/39 (15.38%) 
Neutropenia  1  3/39 (7.69%) 
Thrombocytopenia  1  3/39 (7.69%) 
Cardiac disorders   
Tachicardia  2  2/39 (5.13%) 
Ear and labyrinth disorders   
Tinnitus  1  2/39 (5.13%) 
Vertigo  1  3/39 (7.69%) 
Eye disorders   
Dry eye  1  2/39 (5.13%) 
Keratitis  1  3/39 (7.69%) 
Lacrimation increased  1  6/39 (15.38%) 
Ocular hyperaemia  1  2/39 (5.13%) 
Periorbital oedema  1  2/39 (5.13%) 
Gastrointestinal disorders   
Abdominal pain  1  11/39 (28.21%) 
Abdominal pain upper  1  8/39 (20.51%) 
Constipation  1  7/39 (17.95%) 
Diarrhoea  1  28/39 (71.79%) 
Dry mouth  1  6/39 (15.38%) 
Dyspepsia  1  3/39 (7.69%) 
Gastric disorder  1  3/39 (7.69%) 
Haemorrhoids  1  3/39 (7.69%) 
Nausea  1  17/39 (43.59%) 
Stomatitis  1  2/39 (5.13%) 
Toothache  1  2/39 (5.13%) 
Vomiting  1  21/39 (53.85%) 
Ascites  2  2/39 (5.13%) 
General disorders   
Asthenia  1  15/39 (38.46%) 
Chest pain  1  4/39 (10.26%) 
Fatigue  1  14/39 (35.90%) 
Malaise  1  3/39 (7.69%) 
Mucosal inflammation  1  4/39 (10.26%) 
Oedema peripheral  1  3/39 (7.69%) 
Pyrexia  1  7/39 (17.95%) 
Hepatobiliary disorders   
Hepatocellular injury  1  2/39 (5.13%) 
Infections and infestations   
Nasopharyngitis  1  2/39 (5.13%) 
Urinary tract infection  1  2/39 (5.13%) 
Investigations   
Alanine aminotransferase increased  1  10/39 (25.64%) 
Aspartate aminotransferase increased  1  11/39 (28.21%) 
Blood alkaline phosphatase increased  1  13/39 (33.33%) 
Blood bilirubin increased  1  4/39 (10.26%) 
Blood calcium decreased  1  2/39 (5.13%) 
Blood lactate dehydrogenase increased  1  3/39 (7.69%) 
Blood triglycerides increased  1  2/39 (5.13%) 
C-reactive protein increased  1  2/39 (5.13%) 
Gamma-glutamyltransferase increased  1  14/39 (35.90%) 
Lipase increased  1  4/39 (10.26%) 
Protein total decreased  1  2/39 (5.13%) 
Weight decreased  1  12/39 (30.77%) 
Metabolism and nutrition disorders   
Decreased appetite  1  15/39 (38.46%) 
Dyslipidaemia  1  3/39 (7.69%) 
Hypercholesterolaemia  1  4/39 (10.26%) 
Hyperkalaemia  1  2/39 (5.13%) 
Hypertriglyceridaemia  1  13/39 (33.33%) 
Hypoalbuminaemia  1  7/39 (17.95%) 
Hypocalcaemia  1  4/39 (10.26%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  5/39 (12.82%) 
Muscle spasms  1  3/39 (7.69%) 
Musculoskeletal pain  1  4/39 (10.26%) 
Musculoskeletal stiffness  1  2/39 (5.13%) 
Myalgia  1  3/39 (7.69%) 
Pain in extremity  1  7/39 (17.95%) 
Nervous system disorders   
Dysaesthesia  1  3/39 (7.69%) 
Dysgeusia  1  6/39 (15.38%) 
Headache  1  8/39 (20.51%) 
Neuropathy peripheral  1  2/39 (5.13%) 
Paraesthesia  1  6/39 (15.38%) 
Sciatica  1  4/39 (10.26%) 
Psychiatric disorders   
Anxiety  1  3/39 (7.69%) 
Insomnia  1  4/39 (10.26%) 
Sleep disorder  1  2/39 (5.13%) 
Renal and urinary disorders   
Pollakiuria  1  4/39 (10.26%) 
Proteinuria  1  4/39 (10.26%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  2/39 (5.13%) 
Dysphonia  1  3/39 (7.69%) 
Dyspnoea  1  7/39 (17.95%) 
Epistaxis  1  4/39 (10.26%) 
Skin and subcutaneous tissue disorders   
Dermatitis acneiform  1  2/39 (5.13%) 
Dermatitis allergic  1  2/39 (5.13%) 
Dry skin  1  8/39 (20.51%) 
Pruritus  1  2/39 (5.13%) 
Rash  1  6/39 (15.38%) 
Vascular disorders   
Deep vein thrombosis  1  2/39 (5.13%) 
Hypertension  1  13/39 (33.33%) 
Hypotension  1  2/39 (5.13%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
2
Term from vocabulary, MedDRA 15.1
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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01478373     History of Changes
Other Study ID Numbers: CTKI258AIC02
2011-001725-24 ( EudraCT Number )
First Submitted: November 16, 2011
First Posted: November 23, 2011
Results First Submitted: July 14, 2015
Results First Posted: August 10, 2015
Last Update Posted: April 27, 2016