Safety And Effectiveness Of Daily Dosing With Sunitinib Or Imatinib In Patients With Gastrointestinal Stromal Tumors

Study Overview
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Brief Summary
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A phase IIIb study of patients with gastrointestinal stromal tumors who have had progressive disease while on 400 mg imatinib. Patients will be randomly assigned to either sunitinib 37.5 mg daily or imatinib 800 mg daily. This study will find out the benefits and potential side effects of taking sunitinib or imatinib for approximately one year.

Detailed Description
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The study prematurely discontinued on July 27, 2009 due to poor recruitment and operational futility as a result of changes in clinical practice. There were no safety or efficacy concerns regarding the study in the decision to terminate the trial.

Official Title
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A Phase IIIB, Randomized, Active Controlled Open-Label Study Of Sunitinib (Sutent) 37.5 Mg Daily Vs Imatinib Mesylate 800 Mg Daily In The Treatment Of Patients With Gastrointestinal Stromal Tumors (GIST) Who Have Had Progressive Disease While On 400 Mg Daily Of Imatinib

Conditions
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Gastrointestinal Stromal Tumor

Intervention / Treatment
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* Drug: sunitinib malate
* Drug: imatinib mesylate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with gastrointestinal stromal tumors whose disease has progressed on imatinib 400 mg daily. Exclusion Criteria: Current treatment with any chemotherapy other than imatinib. Current treatment with any dose of imatinib other than 400 mg

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: sunitinib malate<br>* 37.5 mg daily<br>* Other names: Sutent;|
| Active Comparator: B<br> | Drug: imatinib mesylate<br>* 800mg daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | Time from randomization to the first documentation of tumor progression or death due to any cause in the absence of documented tumor progression, whichever was earlier. | Baseline, Week 5, and every 8 weeks until Year 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Time from date of randomization to the date of death. In the absence of confirmation of death, survival time was censored to the last date the participant was known to be alive. | Baseline up to 2 years | 
| Time to Pain Relief Response (TTPR) | Pain relief response defined as a 50 percent (%) or more reduction in the McGill Pain Questionaire - Present Pain Intensity (MPQ-PPI) score (0=no pain to 5=excruciating pain) and/or analgesic use from baseline for at least 3 consecutive weeks. Analgesic use scores were based on 1 point per non narcotic dose of medication and 4 points per dose of narcotic medication. | Day 28 of Cycle 1 up to 26 | 
| Time to Treatment Failure (TTF) | TTF included death for any reason, treatment termination due to intolerable toxicity, or withdrawal of consent, whichever occurred first. | Day 28 of Cycle 1 up to 26 | 
| Number of Participants With Objective Response of Complete Response or Partial Response | Number of participants with objective response based assessment of confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as the disappearance of all target lesions. PR was defined as a greater than or equal to 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. | Day 28 of Cycle 1 up to 26 | 
| Time to Tumor Response (TTR) | Time from date of randomization to first documentation of objective tumor response (partial or complete response). Confirmed complete response (CR) and partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as the disappearance of all target lesions. PR was defined as a greater than or equal to 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. | Day 28 of Cycle 1 up to 26 | 
| Duration of Response (DR) | Time from start of first documentation of objective response(complete or partial response) that was subsequently confirmed to first documentation of objective tumor progression or death due to any cause, whichever occurred first. Confirmed complete response (CR) and partial response (PR)according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as the disappearance of all target lesions. PR was defined as a greater than or equal to 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. | Day 28 of Cycle 1 up to 26 | 
| Time to Pain Progression (TTPP) | TTPP is the number of days from randomization to the first documentation of pain progression (defined as a 50% or more increase in MPQ-PPI score [0=no pain to 5=excruciating pain] or analgesic use from baseline for at least 3 consecutive weeks). Analgesic use scores were based on 1 point per non narcotic dose of medication and 4 points per dose of narcotic medication. | Day 28 of Cycle 1 up to 26 | 
| Number of Participants With Pain Relief Response | Pain relief response defined as a 50% or more reduction in the McGill Pain Questionaire - Present Pain Intensity (MPQ-PPI) score (0=no pain to 5=excruciating pain) and/or analgesic use from baseline for at least 3 consecutive weeks. Analgesic use scores were based on 1 point per non narcotic dose of medication and 4 points per dose of narcotic medication. | Day 28 of Cycle 1 up to 26 | 
| Number of Participants With Pain Progression | Pain progression defined as a 50% or more increase in MPQ-PPI score (0=no pain to 5=excruciating pain) or analgesic use from baseline for at least 3 consecutive weeks. Analgesic use scores were based on 1 point per non narcotic dose of medication and 4 points per dose of narcotic medication. | Day 28 of Cycle 1 up to 26 | 
| Euro Quality of Life (EQ-5D) - Health State Profile Utility Score- Sunitinib Treatment Arm | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component rated current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicated better health state (no problems); 3 indicated worst health state (eg, confined to bed). Scoring formula developed by EuroQol Group assigned utility value for each domain in profile. Score was transformed and results in a total score ranged 0.21 to 1.000; higher score indicated a better health state. | Days 1 and 28 of each cycle | 
| Euro Quality of Life (EQ-5D)- Visual Analog Scale (VAS) - Sunitinib Treatment Arm | EQ-5D: participant rated questionnaire assessed health-related quality of life in terms of a single index value. The VAS component rated current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicated a better health state. | Days 1 and 28 of each cycle | 
| Euro Quality of Life (EQ-5D) - Health State Profile Utility Score - Imatinib Treatment Arm | EQ-5D: participant rated questionnaire assessed health-related quality of life in terms of a single utility score. Health State Profile component rated current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicated better health state (no problems); 3 indicated worst health state (eg, confined to bed). Scoring formula developed by EuroQol Group assigned utility value for each domain in the profile. Score was transformed and results in a total score ranged 0.21 to 1.000; higher score indicated a better health state. | Days 1 and 28 of each cycle | 
| Euro Quality of Life (EQ-5D)- Visual Analog Scale (VAS) - Imatinib Treatment Arm | EQ-5D: participant rated questionnaire assessed health-related quality of life in terms of a single index value. The VAS component rated current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicated a better health state. | Days 1 and 28 of each cycle |