A Study To Assess The Safety And Efficacy Of SU11248 In Patients With Gastrointestinal Stromal Tumor(GIST)

Study Overview
=================
Brief Summary
-----------------
A study to assess the safety and efficacy of SU11248 in patients with gastrointestinal stromal tumor (GIST) whose disease has failed imatinib therapy or who were intolerant to imatinib treatment.

Official Title
-----------------
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study Of SU011248 In The Treatment Of Patients With Imatinib Mesylate (Gleevec Tm, Glivec)-Resistant Or Intolerant Malignant Gastrointestinal Stromal Tumor

Conditions
-----------------
Gastrointestinal Stromal Tumor

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: SU011248


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Histologically-proven diagnosis of malignant GIST not amenable to surgery, radiation or combined modality treatment with curative intent Failed Gleevec treatment or intolerant to Gleevec therapy Key Exclusion Criteria: Treatment with any chemotherapy, chemoembolization therapy, immunotherapy, or investigational agent since the last dose of Gleevec

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: B<br> | Drug: Placebo<br>* 50 mg taken orally once a day. 6 week treatment cycle (Schedule 4/2) 4 weeks on study drug/2 weeks off study drug.<br>|
| Active Comparator: A<br> | Drug: SU011248<br>* 50 mg taken orally once a day. 6 week treatment cycle (Schedule 4/2) 4 weeks on study drug/2 weeks off study drug.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Tumor Progression (TTP) as Assessed by Imaging Studies at End of Double-blind Treatment Phase | Time from randomization to first documentation of objective tumor progression based on the assessment of an independent, third-party imaging laboratory using RECIST (Response Evaluation Criteria in Solid Tumors). | Day 28 of each 6-week cycle : duration of double-blind treatment phase | 
| Time to Tumor Progression (TTP) as Assessed in the Double-blind Treatment Phase at End of Study | Time from randomization to first documentation of objective tumor progression based on the assessment of an independent, third-party imaging laboratory using RECIST (Response Evaluation Criteria in Solid Tumors). | Day 28 of each 6-week cycle : duration of double-blind treatment phase after Last Subject Last Visit (LSLV) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Time from randomization to first documentation of objective tumor progression or to death due to any cause (on treatment or within 28 days of last dose). | Day 28 of each cycle : duration of double-blind treatment phase | 
| Overall Survival Status of Subjects | Number of subjects alive at end of study. | clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug | 
| Overall Survival | Time from date of randomization to date of death due to any cause. | clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug | 
| Overall Survival Based on the Rank Preserving Structural Failure Time Method | time from date of randomization to date of death due to any cause (rank preserving structural failure time method). | clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug | 
| Best Overall Tumor Response During Double-blind Treatment Phase | Tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST). | Day 28 of each cycle : duration of double-blind treatment phase | 
| Confirmed Objective Response (CR or PR) in Subjects | Overall confirmed objective response = confirmed Complete Response (CR) OR confirmed Partial Response (PR) according to RECIST. Confirmed responses were those that persisted on repeat imaging study ≥ 4 weeks after initial documentation of response. | Day 28 of each cycle : duration of double-blind treatment phase | 
| Time to Tumor Response (TTR) | Time from date of randomization to first documentation of objective tumor response that was subsequently confirmed. TTR was only calculated for the subgroup of subjects with a confirmed objective tumor response. | Day 28 of each cycle : duration of double-blind treatment phase | 
| Duration of Performance Status Maintenance | Time from randomization until the last time the performance status was no worse than at baseline or to death due to cancer in the absence of previous documentation of performance status worsening. | Day 28 of each cycle : duration of double-blind treatment phase | 
| Time to Pain Progression Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI) | 25th Quartile: Time to Progression. Progression: a) No change (NC) in MPQ-PPI score (0=no pain to 5=excruciating pain) with increase total analgesic use >= 50% over baseline OR b) Increase score >= 1 point with either NC in total analgesic use or increase total analgesic use >= 50% over baseline. (50th Quartile not achieved.) | Day 1 & 28 of each cycle : duration of double-blind treatment phase | 
| Subjects With Pain Relief Response Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI) | MPQ-PPI: 0=no pain to 5= excruciating pain. Pain Relief Response= 1) Decrease by >= 1 points in MPQ-PPI score with either Decrease or No Change in total analgesic use >= 50% over baseline OR 2) No change in MPQ-PPI score with Decrease total analgesic use >= 50% over baseline. | Day 1 & 28 of each cycle : duration of double-blind treatment phase | 
| Change From Baseline Score in EuroQoL Visual Analog Scale (EQ-VAS) | Change: median score at observation minus median score at baseline. EQ-VAS score on the self-rated thermometer, indicating the patient's own assessment of their health status from 0 (worst) to 100 (best) imaginable health state. | Day 1 & 28 of each cycle : duration of double-blind treatment phase | 
| Change From Baseline in EQ-5D Health State Profile Index | Change: median index score at observation minus median index score at baseline. EQ-5D is a generic instrument that describes health status in 5 dimensions (mobility, self-care, pain/discomfort, anxiety/depression, usual activities) with a weighted health Index based on general population values where where 0.0 = death and 1.0 = perfect health. | Day 1 & 28 of each cycle : duration of double-blind treatment phase |