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Nilotinib 800 Mg And Imatinib 800 Mg For The Treatment Of Patients With Gastrointestinal Stromal Tumors (Gist) Refractory To Imatinib 400 Mg (MACS0375)

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ClinicalTrials.gov Identifier: NCT00751036
Recruitment Status : Terminated
First Posted : September 11, 2008
Results First Posted : March 26, 2014
Last Update Posted : March 26, 2014
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Gastrointestinal Stromal Tumors
Interventions Drug: Nilotinib
Drug: Imatinib
Enrollment 94
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Nilotinib Imatinib
Hide Arm/Group Description Patients who were assigned to this treatment group received 400 mg. nilotinib bid. Patients who were assigned to this treatment group received 400 mg. imatinib bid.
Period Title: Overall Study
Started 48 [1] 46 [1]
Completed 0 [2] 0 [2]
Not Completed 48 46
Reason Not Completed
Disease Progression             28             29
Adverse Event             6             4
Administrative Problems             3             4
Withdrawal by Subject             5             2
Death             3             3
Lost to Follow-up             0             1
Protocol Violation             1             0
Missing end of Treatment Page             2             3
[1]
Started = Treated
[2]
Reason Not Completed = Reason for End of Treatment
Arm/Group Title Nilotinib Imatinib Total
Hide Arm/Group Description Patients who were assigned to this treatment group received 400 mg. nilotinib bid. Patients who were assigned to this treatment group received 400 mg. imatinib bid. Total of all reporting groups
Overall Number of Baseline Participants 48 46 94
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 48 participants 46 participants 94 participants
<65 years 38 35 73
≥ 65 years 9 11 20
Missing 1 0 1
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 46 participants 94 participants
Female
28
  58.3%
19
  41.3%
47
  50.0%
Male
20
  41.7%
27
  58.7%
47
  50.0%
1.Primary Outcome
Title Progression-free Survival (PFS)
Hide Description 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.
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Nilotinib Imatinib
Hide Arm/Group Description:
Patients who were assigned to this treatment group received 400 mg. nilotinib bid.
Patients who were assigned to this treatment group received 400 mg. imatinib bid.
Overall Number of Participants Analyzed 48 46
Median (95% Confidence Interval)
Unit of Measure: Days
111.00
(83.00 to 190.00)
120.00
(59.00 to 173.00)
2.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description 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).
Time Frame every 2 months until 24 months (end of study)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Nilotinib Imatinib
Hide Arm/Group Description:
Patients who were assigned to this treatment group received 400 mg. nilotinib bid.
Patients who were assigned to this treatment group received 400 mg. imatinib bid.
Overall Number of Participants Analyzed 48 46
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Patients
Disease Control Rate (CR, PR, or SD)
54.2
(39.2 to 68.6)
47.8
(32.9 to 63.1)
Complete Response (CR)
2.1
(0.1 to 11.1)
0
(0 to 7.7)
Partial Response (PR)
4.2
(0.5 to 14.3)
6.5
(1.4 to 17.9)
Stable Disease (SD)
47.9
(33.3 to 62.8)
41.3
(27.0 to 56.8)
Progressive Disease (PD)
25.0
(13.6 to 39.6)
37.0
(23.2 to 52.5)
Unknown (UNK)
20.8 [1] 
(NA to NA)
15.2 [1] 
(NA to NA)
[1]
Confidence Interval was not assessed for Unknown.
3.Secondary Outcome
Title Time to Treatment Failure
Hide Description 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’.
Time Frame Time from date of radomization to the earliest date of the first objective tumor, death or discontinuation, assesed until 24 months.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Nilotinib Imatinib
Hide Arm/Group Description:
Patients who were assigned to this treatment group received 400 mg. nilotinib bid.
Patients who were assigned to this treatment group received 400 mg. imatinib bid.
Overall Number of Participants Analyzed 48 46
Median (95% Confidence Interval)
Unit of Measure: Days
90.00
(56.00 to 166.00)
112.00
(58.00 to 171.00)
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description . 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.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Nilotinib Imatinib
Hide Arm/Group Description:
Patients who were assigned to this treatment group received 400 mg. nilotinib bid.
Patients who were assigned to this treatment group received 400 mg. imatinib bid.
Overall Number of Participants Analyzed 48 46
Median (95% Confidence Interval)
Unit of Measure: Days
737 [1] 
(342.00 to NA)
594.00 [1] 
(357.00 to NA)
[1]
Study was terminated early.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Nilotinib 800 mg Imatinib 800 mg
Hide Arm/Group Description Patients who were assigned to this treatment group received 400 mg. nilotinib bid. Patients who were assigned to this treatment group received 400 mg. imatinib bid.
All-Cause Mortality
Nilotinib 800 mg Imatinib 800 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Nilotinib 800 mg Imatinib 800 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   12/48 (25.00%)   10/46 (21.74%) 
Cardiac disorders     
Acute myocardial infarction  1  1/48 (2.08%)  0/46 (0.00%) 
Cardiac failure  1  0/48 (0.00%)  1/46 (2.17%) 
Cardiopulmonary failure  1  1/48 (2.08%)  1/46 (2.17%) 
Tachycardia  1  1/48 (2.08%)  0/46 (0.00%) 
Gastrointestinal disorders     
Abdominal mass  1  0/48 (0.00%)  1/46 (2.17%) 
Abdominal pain  1  2/48 (4.17%)  1/46 (2.17%) 
Duodenal ulcer  1  1/48 (2.08%)  0/46 (0.00%) 
Duodenal ulcer haemorrhage  1  1/48 (2.08%)  0/46 (0.00%) 
Enterocutaneous fistula  1  0/48 (0.00%)  1/46 (2.17%) 
Gastric haemorrhage  1  1/48 (2.08%)  0/46 (0.00%) 
Gastrointestinal haemorrhage  1  0/48 (0.00%)  1/46 (2.17%) 
Gastrointestinal obstruction  1  0/48 (0.00%)  1/46 (2.17%) 
Melaena  1  1/48 (2.08%)  0/46 (0.00%) 
Rectal haemorrhage  1  1/48 (2.08%)  0/46 (0.00%) 
Small intestinal haemorrhage  1  1/48 (2.08%)  0/46 (0.00%) 
General disorders     
Asthenia  1  0/48 (0.00%)  1/46 (2.17%) 
Disease progression  1  2/48 (4.17%)  1/46 (2.17%) 
Drug ineffective  1  1/48 (2.08%)  1/46 (2.17%) 
Performance status decreased  1  0/48 (0.00%)  1/46 (2.17%) 
Hepatobiliary disorders     
Hepatitis acute  1  0/48 (0.00%)  1/46 (2.17%) 
Hepatotoxicity  1  0/48 (0.00%)  1/46 (2.17%) 
Hyperbilirubinaemia  1  0/48 (0.00%)  1/46 (2.17%) 
Infections and infestations     
Bronchopneumonia  1  1/48 (2.08%)  0/46 (0.00%) 
Necrotising fasciitis  1  0/48 (0.00%)  1/46 (2.17%) 
Peritonitis  1  1/48 (2.08%)  0/46 (0.00%) 
Respiratory tract infection  1  1/48 (2.08%)  0/46 (0.00%) 
Septic shock  1  0/48 (0.00%)  1/46 (2.17%) 
Metabolism and nutrition disorders     
Decreased appetite  1  0/48 (0.00%)  1/46 (2.17%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Gastrointestinal stromal tumour  1  2/48 (4.17%)  1/46 (2.17%) 
Neoplasm  1  2/48 (4.17%)  0/46 (0.00%) 
Neoplasm malignant  1  0/48 (0.00%)  1/46 (2.17%) 
Nervous system disorders     
Depressed level of consciousness  1  1/48 (2.08%)  0/46 (0.00%) 
Renal and urinary disorders     
Renal failure  1  1/48 (2.08%)  0/46 (0.00%) 
Urinary retention  1  1/48 (2.08%)  0/46 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  1/48 (2.08%)  1/46 (2.17%) 
Surgical and medical procedures     
Tumour excision  1  1/48 (2.08%)  0/46 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, 15.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Nilotinib 800 mg Imatinib 800 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   39/48 (81.25%)   41/46 (89.13%) 
Blood and lymphatic system disorders     
Anaemia  1  14/48 (29.17%)  15/46 (32.61%) 
Thrombocytopenia  1  1/48 (2.08%)  3/46 (6.52%) 
Eye disorders     
Eyelid oedema  1  0/48 (0.00%)  6/46 (13.04%) 
Gastrointestinal disorders     
Abdominal distension  1  4/48 (8.33%)  7/46 (15.22%) 
Abdominal pain  1  8/48 (16.67%)  11/46 (23.91%) 
Abdominal pain upper  1  4/48 (8.33%)  4/46 (8.70%) 
Ascites  1  0/48 (0.00%)  3/46 (6.52%) 
Constipation  1  7/48 (14.58%)  2/46 (4.35%) 
Diarrhoea  1  4/48 (8.33%)  14/46 (30.43%) 
Dyspepsia  1  2/48 (4.17%)  6/46 (13.04%) 
Nausea  1  12/48 (25.00%)  20/46 (43.48%) 
Vomiting  1  10/48 (20.83%)  13/46 (28.26%) 
General disorders     
Asthenia  1  6/48 (12.50%)  5/46 (10.87%) 
Face oedema  1  0/48 (0.00%)  9/46 (19.57%) 
Fatigue  1  10/48 (20.83%)  12/46 (26.09%) 
Oedema peripheral  1  3/48 (6.25%)  9/46 (19.57%) 
Pyrexia  1  8/48 (16.67%)  5/46 (10.87%) 
Hepatobiliary disorders     
Hyperbilirubinaemia  1  8/48 (16.67%)  0/46 (0.00%) 
Infections and infestations     
Influenza  1  3/48 (6.25%)  1/46 (2.17%) 
Nasopharyngitis  1  1/48 (2.08%)  3/46 (6.52%) 
Upper respiratory tract infection  1  1/48 (2.08%)  3/46 (6.52%) 
Urinary tract infection  1  3/48 (6.25%)  0/46 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  8/48 (16.67%)  1/46 (2.17%) 
Aspartate aminotransferase increased  1  7/48 (14.58%)  1/46 (2.17%) 
Blood albumin decreased  1  3/48 (6.25%)  1/46 (2.17%) 
Blood alkaline phosphatase increased  1  4/48 (8.33%)  0/46 (0.00%) 
Blood bilirubin increased  1  8/48 (16.67%)  0/46 (0.00%) 
Blood calcium decreased  1  0/48 (0.00%)  3/46 (6.52%) 
Blood potassium decreased  1  1/48 (2.08%)  6/46 (13.04%) 
Gamma-glutamyltransferase increased  1  3/48 (6.25%)  0/46 (0.00%) 
Neutrophil count decreased  1  2/48 (4.17%)  4/46 (8.70%) 
White blood cell count decreased  1  2/48 (4.17%)  8/46 (17.39%) 
Metabolism and nutrition disorders     
Decreased appetite  1  6/48 (12.50%)  10/46 (21.74%) 
Hyperglycaemia  1  5/48 (10.42%)  1/46 (2.17%) 
Hypokalaemia  1  0/48 (0.00%)  3/46 (6.52%) 
Hypophosphataemia  1  2/48 (4.17%)  6/46 (13.04%) 
Musculoskeletal and connective tissue disorders     
Myalgia  1  3/48 (6.25%)  1/46 (2.17%) 
Pain in extremity  1  2/48 (4.17%)  3/46 (6.52%) 
Nervous system disorders     
Dizziness  1  1/48 (2.08%)  3/46 (6.52%) 
Headache  1  8/48 (16.67%)  2/46 (4.35%) 
Renal and urinary disorders     
Dysuria  1  3/48 (6.25%)  2/46 (4.35%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  3/48 (6.25%)  2/46 (4.35%) 
Dyspnoea  1  3/48 (6.25%)  1/46 (2.17%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  5/48 (10.42%)  1/46 (2.17%) 
Rash  1  8/48 (16.67%)  2/46 (4.35%) 
Vascular disorders     
Hypertension  1  1/48 (2.08%)  3/46 (6.52%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, 15.1
Patients were limited (planned 300, Actual 94). Early termination of study; not sufficient power to test the original primary hypothesis with respect to PFS. Only descriptive analyses were carried out for this study.
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.

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.

Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00751036     History of Changes
Other Study ID Numbers: CAMN107DBR01
2010-019806-18
First Submitted: September 9, 2008
First Posted: September 11, 2008
Results First Submitted: October 29, 2013
Results First Posted: March 26, 2014
Last Update Posted: March 26, 2014