Study Of SU011248 Administered On A Continuous Daily Dosing Schedule In Patients With Gastrointestinal Stromal Tumor

Study Overview
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Brief Summary
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To evaluate the antitumor activity of SU011248 in advanced, imatinib mesylate-resistant gastrointestinal stromal tumor (GIST) when administered on a continuous daily dosing schedule

Detailed Description
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Subjects experiencing clinical benefit after 1 year on study were offered continued treatment with SU011248 on a separate protocol.

Official Title
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A Phase 2 Efficacy And Safety Study Of SU011248 Administered In A Continuous Daily Regimen In Patients With Advanced Gastrointestinal Stromal Tumor

Conditions
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Gastrointestinal Stromal Tumors

Intervention / Treatment
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* Drug: SU011248


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathologically proven diagnosis of malignant GIST that was not amenable to standard therapy. Failed prior treatment with imatinib mesylate, defined either by progression of disease (according to Response Evaluation Criterion in Solid Tumors (RECIST) or World Health Organization (WHO) criteria), or by significant toxicity during treatment with imatinib mesylate that precluded further treatment. Intolerance to prior imatinib mesylate therapy was defined as follows: Life-threatening adverse events (ie, Grade 4) at any dose (attempt to dose reduce or rechallenge not required) or Unacceptable toxicity induced by a moderate dose (eg, 400 mg/day), specifically, Grade 2 toxicity that was unacceptable to the patient (such as nausea) that persisted despite standard countermeasures Evidence of unidimensionally measurable disease. Exclusion Criteria: Previous treatment on a SU011248 clinical trial. Diagnosis of any second malignancy within the last 3 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma, that had been adequately treated with no evidence of recurrent disease for 12 months. History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease. Any of the following within the 12 months prior to starting the study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism. Ongoing cardiac dysrhythmias of grade 2, atrial fibrillation of any grade, or QTc interval >450 msec for males or >470 msec for females. Hypertension that could not be controlled by medications (>150/100 mm/Hg despite optimal medical therapy).

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: SU011248<br>* 37.5 mg once daily on a continuous daily dosing schedule. Study medication continued as long as patient was obtaining clinical benefit, or until significant toxicity, or withdrawal of consent, for up to 1 year on study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Benefit Response (CBR) According to RECIST | CBR is defined as a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) for at least 24 weeks on study according to RECIST. Confirmed responses are those that persisted on repeat imaging >= 4 wks after initial response. Participants with no on-study radiographic tumor re-evaluation counted as non-responders. | Planned duration on this protocol of up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants by Best Confirmed Response Category According to RECIST | Best confirmed response (BCR) defined as best response [confirmed CR, confirmed PR, SD, PD(progressive disease), not evaluable (NE)] recorded from start of treatment until disease progression / recurrence. Best response of SD must have met SD criteria at least once after first dose at minimum interval of 6 weeks. | Planned duration on this protocol of up to 1 year | 
| Number of Participants With Overall Confirmed Objective Disease Response (ORR) | Overall confirmed objective disease response is defined as a confirmed CR, or confirmed PR according to RECIST. Confirmed responses are those that persisted on repeat imaging >= 4 wks after initial response. | Planned duration on this protocol of up to 1 year | 
| Duration of Stable Disease | Duration of SD is the time from the date of first documentation of stable disease to the date of first documentation of objective tumor progression or death due to any cause that occurred within 28 days after last dose of study medication, whichever occurred first. | Planned duration on this protocol of up to 1 year | 
| Progression-free Survival (PFS) | PFS was defined as the time from the date of first dose of study medication to the date of first documentation of objective tumor progression or to death due to any cause that occurred on treatment including within 28 days after the last dose of study medication, whichever occurred first. | Planned duration on this protocol of up to 1 year | 
| Time to Tumor Progression (TTP) | TTP was defined as the time from the date of first dose of study medication to the date of first documentation of objective tumor progression that occurred on treatment including within 28 days after the last dose of study medication. | Planned duration on this protocol of up to 1 year | 
| Duration of Tumor Response (DR) [Descriptive Statistics] | DR was defined as the time from the date of first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the date of the first documentation of objective tumor progression or to death due to any cause that occurred within 28 days after the last dose of study medication, whichever occurred first. | Planned duration on this protocol of up to 1 year | 
| Overall Survival (OS) and One-year Survival [Descriptive Statistics] | Overall survival is defined as time from the date of first dose of study medication to the date of death due to any cause. One year survival rate defined as the probability that a patient is alive 1 year after the date of first study medication. | Survival status was collected by telephone contact every 2 months for up to 2 years from study entry. | 
| Score of FACIT-Fatigue Scale | FACIT-Fatigue Scale: Overall score from 13-question questionnaire (measures fatigue/asthenia for patients with chronic, life-threatening illnesses). For each question, patient rates condition for the past week on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). Maximum, minimum mean included data available for >=10 subjects. | Baseline, Day 1 & 15 of each treatment cycle | 
| Score of EQ-VAS (Euro Quality of Life -Visual Analog Scale) | 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. Change: median score at observation minus median score at baseline. Maximum changes (Increase or Decrease from baseline) included data available for >=10 subjects. | Baseline, Day 1 &15 of each treatment cycle up to 1 year on study | 
| Score of EQ-5D (Euro Quality of Life-5 Dimension) Weighted Health Index | EQ-5D: 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 0.0 = death and 1.0 = perfect health. Change: median index score at observation minus median index score at baseline (includes data available for >=10 subjects). | Baseline, Day 1 & 15 of each treatment cycle up to 1 year on study |