Trial Outcomes & Findings for Efficacy and Safety of Dovitinib in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib (NCT NCT01478373)
NCT ID: NCT01478373
Last Updated: 2016-04-27
Results Overview
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.
COMPLETED
PHASE2
39 participants
12 Weeks
2016-04-27
Participant Flow
39 Patients enrolled. One patient had a protocol deviation which excluded him from the Full Analysis Set.
Participant milestones
| Measure |
Dovitinib
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.
|
|---|---|
|
Treatment Phase
STARTED
|
39
|
|
Treatment Phase
COMPLETED
|
38
|
|
Treatment Phase
NOT COMPLETED
|
1
|
|
Survival Phase
STARTED
|
38
|
|
Survival Phase
COMPLETED
|
0
|
|
Survival Phase
NOT COMPLETED
|
38
|
Reasons for withdrawal
| Measure |
Dovitinib
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.
|
|---|---|
|
Treatment Phase
Protocol Violation
|
1
|
|
Survival Phase
Adverse Event
|
8
|
|
Survival Phase
Protocol Violation
|
1
|
|
Survival Phase
crossover to another study
|
2
|
|
Survival Phase
Progressive Disease
|
27
|
Baseline Characteristics
Efficacy and Safety of Dovitinib in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib
Baseline characteristics by cohort
| Measure |
Dovitinib
n=38 Participants
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.
|
|---|---|
|
Age, Continuous
|
59.2 Years
STANDARD_DEVIATION 10.14 • n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 WeeksPopulation: Full Analysis Set: all subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.
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.
Outcome measures
| Measure |
Dovitinib
n=38 Participants
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.
|
|---|---|
|
Antitumor Activity of Dovitinib in Terms of Disease Control Rate (DCR): Complete Response+Partial Response +Stable Disease
|
52.6 Percentage of Participants
Interval 38.2 to 66.7
|
SECONDARY outcome
Timeframe: 9 monthsPopulation: Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.
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.
Outcome measures
| Measure |
Dovitinib
n=38 Participants
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.
|
|---|---|
|
Progression-free Survival (PFS) of Patients Treated With Dovitinib
|
141 Days
Interval 86.0 to 225.0
|
SECONDARY outcome
Timeframe: 9 monthsPopulation: Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.
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'.
Outcome measures
| Measure |
Dovitinib
n=38 Participants
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.
|
|---|---|
|
Time to Treatment Failure (TTF)of Patients Treated With Dovitinib
|
122.0 Days
Interval 81.0 to 223.0
|
SECONDARY outcome
Timeframe: 9 monthsPopulation: Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.
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.
Outcome measures
| Measure |
Dovitinib
n=38 Participants
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.
|
|---|---|
|
Duration of Response or Stable Disease (SD)
|
193.2 Days
Standard Deviation 117.78
|
SECONDARY outcome
Timeframe: 9 monthsPopulation: Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.
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.
Outcome measures
| Measure |
Dovitinib
n=38 Participants
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.
|
|---|---|
|
Time to Tumor Progression (TTP)of Patients Treated With Dovitinib
|
141.0 Days
Interval 85.0 to 229.0
|
SECONDARY outcome
Timeframe: Baseline, 12 weeksPopulation: Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.
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.
Outcome measures
| Measure |
Dovitinib
n=38 Participants
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 Response Rate (ORR) of Patients Treated With Dovitinib
|
2.6 Percentage of Participants
Interval 0.1 to 11.9
|
SECONDARY outcome
Timeframe: 21 months (9 months of estimated treatment plus 12 months of survival follow up)Population: Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.
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.
Outcome measures
| Measure |
Dovitinib
n=38 Participants
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 Survival (OS) of Patients Treated With Dovitinib
|
NA Months
The median survival had not been reached
|
SECONDARY outcome
Timeframe: Up to 9 months of estimated treatmentPopulation: Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.
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.
Outcome measures
| Measure |
Dovitinib
n=38 Participants
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.
|
|---|---|
|
DCR (CR+PR+SD) at the End of Treatment
|
52.6 Percentage of Participants
Interval 38.2 to 66.7
|
Adverse Events
Dovitinib
Serious adverse events
| Measure |
Dovitinib
n=39 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
2.6%
1/39
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.6%
1/39
|
|
Blood and lymphatic system disorders
Pancytopenia
|
2.6%
1/39
|
|
Cardiac disorders
Cardiac arrest
|
2.6%
1/39
|
|
Cardiac disorders
Tachycardia
|
2.6%
1/39
|
|
Gastrointestinal disorders
Abdominal pain
|
2.6%
1/39
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.6%
1/39
|
|
Gastrointestinal disorders
Ascites
|
2.6%
1/39
|
|
Gastrointestinal disorders
Diarrhoea
|
5.1%
2/39
|
|
Gastrointestinal disorders
Nausea
|
2.6%
1/39
|
|
Gastrointestinal disorders
Peritoneal haemorrhage
|
2.6%
1/39
|
|
Gastrointestinal disorders
Vomiting
|
7.7%
3/39
|
|
General disorders
Asthenia
|
2.6%
1/39
|
|
General disorders
Fatigue
|
10.3%
4/39
|
|
General disorders
General physical health deterioration
|
2.6%
1/39
|
|
General disorders
Inflammation
|
2.6%
1/39
|
|
General disorders
Localised oedema
|
2.6%
1/39
|
|
General disorders
Mucosal dryness
|
2.6%
1/39
|
|
General disorders
Oedema peripheral
|
2.6%
1/39
|
|
General disorders
Systemic inflammatory response syndrome
|
2.6%
1/39
|
|
Hepatobiliary disorders
Cholestasis
|
2.6%
1/39
|
|
Infections and infestations
H1N1 influenza
|
2.6%
1/39
|
|
Infections and infestations
Tracheobronchitis
|
2.6%
1/39
|
|
Investigations
Red blood cell count decreased
|
2.6%
1/39
|
|
Investigations
Weight decreased
|
2.6%
1/39
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.1%
2/39
|
|
Metabolism and nutrition disorders
Dehydration
|
2.6%
1/39
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
2.6%
1/39
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
2.6%
1/39
|
|
Nervous system disorders
Neuropathy peripheral
|
2.6%
1/39
|
|
Nervous system disorders
Paraesthesia
|
2.6%
1/39
|
|
Psychiatric disorders
Mania
|
2.6%
1/39
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
2.6%
1/39
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.6%
1/39
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
2.6%
1/39
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
2.6%
1/39
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
5.1%
2/39
|
|
Skin and subcutaneous tissue disorders
Toxic skin eruption
|
2.6%
1/39
|
|
Vascular disorders
Aortic thrombosis
|
2.6%
1/39
|
|
Vascular disorders
Phlebitis
|
2.6%
1/39
|
Other adverse events
| Measure |
Dovitinib
n=39 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
15.4%
6/39
|
|
Blood and lymphatic system disorders
Neutropenia
|
7.7%
3/39
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
7.7%
3/39
|
|
Ear and labyrinth disorders
Tinnitus
|
5.1%
2/39
|
|
Ear and labyrinth disorders
Vertigo
|
7.7%
3/39
|
|
Eye disorders
Dry eye
|
5.1%
2/39
|
|
Eye disorders
Keratitis
|
7.7%
3/39
|
|
Eye disorders
Lacrimation increased
|
15.4%
6/39
|
|
Eye disorders
Ocular hyperaemia
|
5.1%
2/39
|
|
Eye disorders
Periorbital oedema
|
5.1%
2/39
|
|
Gastrointestinal disorders
Abdominal pain
|
28.2%
11/39
|
|
Gastrointestinal disorders
Abdominal pain upper
|
20.5%
8/39
|
|
Gastrointestinal disorders
Constipation
|
17.9%
7/39
|
|
Gastrointestinal disorders
Diarrhoea
|
71.8%
28/39
|
|
Gastrointestinal disorders
Dry mouth
|
15.4%
6/39
|
|
Gastrointestinal disorders
Dyspepsia
|
7.7%
3/39
|
|
Gastrointestinal disorders
Gastric disorder
|
7.7%
3/39
|
|
Gastrointestinal disorders
Haemorrhoids
|
7.7%
3/39
|
|
Gastrointestinal disorders
Nausea
|
43.6%
17/39
|
|
Gastrointestinal disorders
Stomatitis
|
5.1%
2/39
|
|
Gastrointestinal disorders
Toothache
|
5.1%
2/39
|
|
Gastrointestinal disorders
Vomiting
|
53.8%
21/39
|
|
General disorders
Asthenia
|
38.5%
15/39
|
|
General disorders
Chest pain
|
10.3%
4/39
|
|
General disorders
Fatigue
|
35.9%
14/39
|
|
General disorders
Malaise
|
7.7%
3/39
|
|
General disorders
Mucosal inflammation
|
10.3%
4/39
|
|
General disorders
Oedema peripheral
|
7.7%
3/39
|
|
General disorders
Pyrexia
|
17.9%
7/39
|
|
Hepatobiliary disorders
Hepatocellular injury
|
5.1%
2/39
|
|
Infections and infestations
Nasopharyngitis
|
5.1%
2/39
|
|
Infections and infestations
Urinary tract infection
|
5.1%
2/39
|
|
Investigations
Alanine aminotransferase increased
|
25.6%
10/39
|
|
Investigations
Aspartate aminotransferase increased
|
28.2%
11/39
|
|
Investigations
Blood alkaline phosphatase increased
|
33.3%
13/39
|
|
Investigations
Blood bilirubin increased
|
10.3%
4/39
|
|
Investigations
Blood calcium decreased
|
5.1%
2/39
|
|
Investigations
Blood lactate dehydrogenase increased
|
7.7%
3/39
|
|
Investigations
Blood triglycerides increased
|
5.1%
2/39
|
|
Investigations
C-reactive protein increased
|
5.1%
2/39
|
|
Investigations
Gamma-glutamyltransferase increased
|
35.9%
14/39
|
|
Investigations
Lipase increased
|
10.3%
4/39
|
|
Investigations
Protein total decreased
|
5.1%
2/39
|
|
Investigations
Weight decreased
|
30.8%
12/39
|
|
Metabolism and nutrition disorders
Decreased appetite
|
38.5%
15/39
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
7.7%
3/39
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
10.3%
4/39
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
5.1%
2/39
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
33.3%
13/39
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
17.9%
7/39
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
10.3%
4/39
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.8%
5/39
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
7.7%
3/39
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
10.3%
4/39
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
5.1%
2/39
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.7%
3/39
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
17.9%
7/39
|
|
Nervous system disorders
Dysaesthesia
|
7.7%
3/39
|
|
Nervous system disorders
Dysgeusia
|
15.4%
6/39
|
|
Nervous system disorders
Headache
|
20.5%
8/39
|
|
Nervous system disorders
Neuropathy peripheral
|
5.1%
2/39
|
|
Nervous system disorders
Paraesthesia
|
15.4%
6/39
|
|
Nervous system disorders
Sciatica
|
10.3%
4/39
|
|
Psychiatric disorders
Anxiety
|
7.7%
3/39
|
|
Psychiatric disorders
Insomnia
|
10.3%
4/39
|
|
Psychiatric disorders
Sleep disorder
|
5.1%
2/39
|
|
Renal and urinary disorders
Pollakiuria
|
10.3%
4/39
|
|
Renal and urinary disorders
Proteinuria
|
10.3%
4/39
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.1%
2/39
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
7.7%
3/39
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
17.9%
7/39
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
10.3%
4/39
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
5.1%
2/39
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
5.1%
2/39
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
20.5%
8/39
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.1%
2/39
|
|
Skin and subcutaneous tissue disorders
Rash
|
15.4%
6/39
|
|
Vascular disorders
Deep vein thrombosis
|
5.1%
2/39
|
|
Vascular disorders
Hypertension
|
33.3%
13/39
|
|
Vascular disorders
Hypotension
|
5.1%
2/39
|
|
Cardiac disorders
Tachicardia
|
5.1%
2/39
|
|
Gastrointestinal disorders
Ascites
|
5.1%
2/39
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER