Trial Outcomes & Findings for Nilotinib 800 Mg And Imatinib 800 Mg For The Treatment Of Patients With Gastrointestinal Stromal Tumors (Gist) Refractory To Imatinib 400 Mg (NCT NCT00751036)
NCT ID: NCT00751036
Last Updated: 2014-03-26
Results Overview
Progression-free survival (PFS) is the time from date of randomization to the date of first documented progression or death due to any cause. If a participant has not had an event, progression-free survival is censored at the time of last adequate tumor assessment. Progression is defined according to modified RECIST criteria as at least a 20% increase in the sum of the longest diameter of target lesions, worsening of the non-target lesions or the appearance of one or more new lesions.
TERMINATED
PHASE3
94 participants
24 months
2014-03-26
Participant Flow
Participant milestones
| Measure |
Nilotinib
Patients who were assigned to this treatment group received 400 mg. nilotinib bid.
|
Imatinib
Patients who were assigned to this treatment group received 400 mg. imatinib bid.
|
|---|---|---|
|
Overall Study
STARTED
|
48
|
46
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
48
|
46
|
Reasons for withdrawal
| Measure |
Nilotinib
Patients who were assigned to this treatment group received 400 mg. nilotinib bid.
|
Imatinib
Patients who were assigned to this treatment group received 400 mg. imatinib bid.
|
|---|---|---|
|
Overall Study
Disease Progression
|
28
|
29
|
|
Overall Study
Adverse Event
|
6
|
4
|
|
Overall Study
Administrative Problems
|
3
|
4
|
|
Overall Study
Withdrawal by Subject
|
5
|
2
|
|
Overall Study
Death
|
3
|
3
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Missing end of Treatment Page
|
2
|
3
|
Baseline Characteristics
Nilotinib 800 Mg And Imatinib 800 Mg For The Treatment Of Patients With Gastrointestinal Stromal Tumors (Gist) Refractory To Imatinib 400 Mg
Baseline characteristics by cohort
| Measure |
Nilotinib
n=48 Participants
Patients who were assigned to this treatment group received 400 mg. nilotinib bid.
|
Imatinib
n=46 Participants
Patients who were assigned to this treatment group received 400 mg. imatinib bid.
|
Total
n=94 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
<65 years
|
38 Participants
n=99 Participants
|
35 Participants
n=107 Participants
|
73 Participants
n=206 Participants
|
|
Age, Customized
≥ 65 years
|
9 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Age, Customized
Missing
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=99 Participants
|
19 Participants
n=107 Participants
|
47 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=99 Participants
|
27 Participants
n=107 Participants
|
47 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 24 monthsPopulation: Full Analysis Set (FAS) consisted of all randomized patients. Following the intent to treat principle, patients were analyzed according to the treatment which they were assigned at randomization.
Progression-free survival (PFS) is the time from date of randomization to the date of first documented progression or death due to any cause. If a participant has not had an event, progression-free survival is censored at the time of last adequate tumor assessment. Progression is defined according to modified RECIST criteria as at least a 20% increase in the sum of the longest diameter of target lesions, worsening of the non-target lesions or the appearance of one or more new lesions.
Outcome measures
| Measure |
Nilotinib
n=48 Participants
Patients who were assigned to this treatment group received 400 mg. nilotinib bid.
|
Imatinib
n=46 Participants
Patients who were assigned to this treatment group received 400 mg. imatinib bid.
|
|---|---|---|
|
Progression-free Survival (PFS)
|
111.00 Days
Interval 83.0 to 190.0
|
120.00 Days
Interval 59.0 to 173.0
|
SECONDARY outcome
Timeframe: every 2 months until 24 months (end of study)Population: Full analysis set (FAS): consisted of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment to which they were assigned at randomization.
The Disease Control Rate (Complete Response(CR), Partial Response (PD) and Stable Disease (SD) rates for each treatment arm will be computed using the exact Clopper-Pearson interval estimation methodology. DCR is defined as the percentage of patients with a best overall response of • CR, i.e. at least two determinations of CR at least 4 weeks apart without loss of response between the determinations, • PR, i.e. at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) and without loss of PR between the determinations, or • SD lasting at least 24 weeks, i.e. at least one SD or better response at least 24 weeks after randomization (and not qualifying for CR or PR).
Outcome measures
| Measure |
Nilotinib
n=48 Participants
Patients who were assigned to this treatment group received 400 mg. nilotinib bid.
|
Imatinib
n=46 Participants
Patients who were assigned to this treatment group received 400 mg. imatinib bid.
|
|---|---|---|
|
Disease Control Rate (DCR)
Complete Response (CR)
|
2.1 Percentage of Patients
Interval 0.1 to 11.1
|
0 Percentage of Patients
Interval 0.0 to 7.7
|
|
Disease Control Rate (DCR)
Disease Control Rate (CR, PR, or SD)
|
54.2 Percentage of Patients
Interval 39.2 to 68.6
|
47.8 Percentage of Patients
Interval 32.9 to 63.1
|
|
Disease Control Rate (DCR)
Partial Response (PR)
|
4.2 Percentage of Patients
Interval 0.5 to 14.3
|
6.5 Percentage of Patients
Interval 1.4 to 17.9
|
|
Disease Control Rate (DCR)
Stable Disease (SD)
|
47.9 Percentage of Patients
Interval 33.3 to 62.8
|
41.3 Percentage of Patients
Interval 27.0 to 56.8
|
|
Disease Control Rate (DCR)
Progressive Disease (PD)
|
25.0 Percentage of Patients
Interval 13.6 to 39.6
|
37.0 Percentage of Patients
Interval 23.2 to 52.5
|
|
Disease Control Rate (DCR)
Unknown (UNK)
|
20.8 Percentage of Patients
Confidence Interval was not assessed for Unknown.
|
15.2 Percentage of Patients
Confidence Interval was not assessed for Unknown.
|
SECONDARY outcome
Timeframe: Time from date of radomization to the earliest date of the first objective tumor, death or discontinuation, assesed until 24 months.Population: Full analysis set (FAS): consisted of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment to which they were assigned at randomization.
TTF, defined as the time from date of randomization to the earliest of 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 |
Nilotinib
n=48 Participants
Patients who were assigned to this treatment group received 400 mg. nilotinib bid.
|
Imatinib
n=46 Participants
Patients who were assigned to this treatment group received 400 mg. imatinib bid.
|
|---|---|---|
|
Time to Treatment Failure
|
90.00 Days
Interval 56.0 to 166.0
|
112.00 Days
Interval 58.0 to 171.0
|
SECONDARY outcome
Timeframe: time from the date of randomization to the date of death due to any cause or the date of last contact prior to or on the date of data cutoff, assesed until 24 months.Population: Full analysis set (FAS): consisted of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment to which they were assigned at randomization.
. OS is defined as the time from the date of randomization to the date of death due to any cause or the date of last contact prior to or on the date of data cutoff. The median time to overall survival and its associated 95 % CI will be derived, for each treatment arm, using the time to event analysis based on Kaplan-Meier methodology.
Outcome measures
| Measure |
Nilotinib
n=48 Participants
Patients who were assigned to this treatment group received 400 mg. nilotinib bid.
|
Imatinib
n=46 Participants
Patients who were assigned to this treatment group received 400 mg. imatinib bid.
|
|---|---|---|
|
Overall Survival (OS)
|
737 Days
Interval 342.0 to
Study was terminated early.
|
594.00 Days
Interval 357.0 to
Study was terminated early.
|
Adverse Events
Nilotinib 800 mg
Imatinib 800 mg
Serious adverse events
| Measure |
Nilotinib 800 mg
n=48 participants at risk
Patients who were assigned to this treatment group received 400 mg. nilotinib bid.
|
Imatinib 800 mg
n=46 participants at risk
Patients who were assigned to this treatment group received 400 mg. imatinib bid.
|
|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
2.1%
1/48
|
0.00%
0/46
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/48
|
2.2%
1/46
|
|
Cardiac disorders
Cardiopulmonary failure
|
2.1%
1/48
|
2.2%
1/46
|
|
Cardiac disorders
Tachycardia
|
2.1%
1/48
|
0.00%
0/46
|
|
Gastrointestinal disorders
Abdominal mass
|
0.00%
0/48
|
2.2%
1/46
|
|
Gastrointestinal disorders
Abdominal pain
|
4.2%
2/48
|
2.2%
1/46
|
|
Gastrointestinal disorders
Duodenal ulcer
|
2.1%
1/48
|
0.00%
0/46
|
|
Gastrointestinal disorders
Duodenal ulcer haemorrhage
|
2.1%
1/48
|
0.00%
0/46
|
|
Gastrointestinal disorders
Enterocutaneous fistula
|
0.00%
0/48
|
2.2%
1/46
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
2.1%
1/48
|
0.00%
0/46
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/48
|
2.2%
1/46
|
|
Gastrointestinal disorders
Gastrointestinal obstruction
|
0.00%
0/48
|
2.2%
1/46
|
|
Gastrointestinal disorders
Melaena
|
2.1%
1/48
|
0.00%
0/46
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
2.1%
1/48
|
0.00%
0/46
|
|
Gastrointestinal disorders
Small intestinal haemorrhage
|
2.1%
1/48
|
0.00%
0/46
|
|
General disorders
Asthenia
|
0.00%
0/48
|
2.2%
1/46
|
|
General disorders
Disease progression
|
4.2%
2/48
|
2.2%
1/46
|
|
General disorders
Drug ineffective
|
2.1%
1/48
|
2.2%
1/46
|
|
General disorders
Performance status decreased
|
0.00%
0/48
|
2.2%
1/46
|
|
Hepatobiliary disorders
Hepatitis acute
|
0.00%
0/48
|
2.2%
1/46
|
|
Hepatobiliary disorders
Hepatotoxicity
|
0.00%
0/48
|
2.2%
1/46
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/48
|
2.2%
1/46
|
|
Infections and infestations
Bronchopneumonia
|
2.1%
1/48
|
0.00%
0/46
|
|
Infections and infestations
Necrotising fasciitis
|
0.00%
0/48
|
2.2%
1/46
|
|
Infections and infestations
Peritonitis
|
2.1%
1/48
|
0.00%
0/46
|
|
Infections and infestations
Respiratory tract infection
|
2.1%
1/48
|
0.00%
0/46
|
|
Infections and infestations
Septic shock
|
0.00%
0/48
|
2.2%
1/46
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/48
|
2.2%
1/46
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrointestinal stromal tumour
|
4.2%
2/48
|
2.2%
1/46
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm
|
4.2%
2/48
|
0.00%
0/46
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm malignant
|
0.00%
0/48
|
2.2%
1/46
|
|
Nervous system disorders
Depressed level of consciousness
|
2.1%
1/48
|
0.00%
0/46
|
|
Renal and urinary disorders
Renal failure
|
2.1%
1/48
|
0.00%
0/46
|
|
Renal and urinary disorders
Urinary retention
|
2.1%
1/48
|
0.00%
0/46
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.1%
1/48
|
2.2%
1/46
|
|
Surgical and medical procedures
Tumour excision
|
2.1%
1/48
|
0.00%
0/46
|
Other adverse events
| Measure |
Nilotinib 800 mg
n=48 participants at risk
Patients who were assigned to this treatment group received 400 mg. nilotinib bid.
|
Imatinib 800 mg
n=46 participants at risk
Patients who were assigned to this treatment group received 400 mg. imatinib bid.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
29.2%
14/48
|
32.6%
15/46
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.1%
1/48
|
6.5%
3/46
|
|
Eye disorders
Eyelid oedema
|
0.00%
0/48
|
13.0%
6/46
|
|
Gastrointestinal disorders
Abdominal distension
|
8.3%
4/48
|
15.2%
7/46
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
8/48
|
23.9%
11/46
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.3%
4/48
|
8.7%
4/46
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/48
|
6.5%
3/46
|
|
Gastrointestinal disorders
Constipation
|
14.6%
7/48
|
4.3%
2/46
|
|
Gastrointestinal disorders
Diarrhoea
|
8.3%
4/48
|
30.4%
14/46
|
|
Gastrointestinal disorders
Dyspepsia
|
4.2%
2/48
|
13.0%
6/46
|
|
Gastrointestinal disorders
Nausea
|
25.0%
12/48
|
43.5%
20/46
|
|
Gastrointestinal disorders
Vomiting
|
20.8%
10/48
|
28.3%
13/46
|
|
General disorders
Asthenia
|
12.5%
6/48
|
10.9%
5/46
|
|
General disorders
Face oedema
|
0.00%
0/48
|
19.6%
9/46
|
|
General disorders
Fatigue
|
20.8%
10/48
|
26.1%
12/46
|
|
General disorders
Oedema peripheral
|
6.2%
3/48
|
19.6%
9/46
|
|
General disorders
Pyrexia
|
16.7%
8/48
|
10.9%
5/46
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
16.7%
8/48
|
0.00%
0/46
|
|
Infections and infestations
Influenza
|
6.2%
3/48
|
2.2%
1/46
|
|
Infections and infestations
Nasopharyngitis
|
2.1%
1/48
|
6.5%
3/46
|
|
Infections and infestations
Upper respiratory tract infection
|
2.1%
1/48
|
6.5%
3/46
|
|
Infections and infestations
Urinary tract infection
|
6.2%
3/48
|
0.00%
0/46
|
|
Investigations
Alanine aminotransferase increased
|
16.7%
8/48
|
2.2%
1/46
|
|
Investigations
Aspartate aminotransferase increased
|
14.6%
7/48
|
2.2%
1/46
|
|
Investigations
Blood albumin decreased
|
6.2%
3/48
|
2.2%
1/46
|
|
Investigations
Blood alkaline phosphatase increased
|
8.3%
4/48
|
0.00%
0/46
|
|
Investigations
Blood bilirubin increased
|
16.7%
8/48
|
0.00%
0/46
|
|
Investigations
Blood calcium decreased
|
0.00%
0/48
|
6.5%
3/46
|
|
Investigations
Blood potassium decreased
|
2.1%
1/48
|
13.0%
6/46
|
|
Investigations
Gamma-glutamyltransferase increased
|
6.2%
3/48
|
0.00%
0/46
|
|
Investigations
Neutrophil count decreased
|
4.2%
2/48
|
8.7%
4/46
|
|
Investigations
White blood cell count decreased
|
4.2%
2/48
|
17.4%
8/46
|
|
Metabolism and nutrition disorders
Decreased appetite
|
12.5%
6/48
|
21.7%
10/46
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
10.4%
5/48
|
2.2%
1/46
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/48
|
6.5%
3/46
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
4.2%
2/48
|
13.0%
6/46
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.2%
3/48
|
2.2%
1/46
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
4.2%
2/48
|
6.5%
3/46
|
|
Nervous system disorders
Dizziness
|
2.1%
1/48
|
6.5%
3/46
|
|
Nervous system disorders
Headache
|
16.7%
8/48
|
4.3%
2/46
|
|
Renal and urinary disorders
Dysuria
|
6.2%
3/48
|
4.3%
2/46
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.2%
3/48
|
4.3%
2/46
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
6.2%
3/48
|
2.2%
1/46
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.4%
5/48
|
2.2%
1/46
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.7%
8/48
|
4.3%
2/46
|
|
Vascular disorders
Hypertension
|
2.1%
1/48
|
6.5%
3/46
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee Principal Investigators are NOT employed by the organization sponsoring the study. Other disclosure agreement that restricts the right of the PI 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.
- Publication restrictions are in place
Restriction type: OTHER