Inclusion Criteria:

• Histopathologically proven diagnosis of malignant GIST that is not amenable to standard therapy.
• Failed prior treatment with imatinib mesylate, defined either by progression of disease (according to RECIST or WHO criteria), or by significant toxicity during treatment with imatinib mesylate that precluded further treatment. Intolerance to prior imatinib mesylate therapy will be 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 is unacceptable to the patient (such as nausea) that persists despite standard countermeasures
• Evidence of unidimensionally measurable disease.
• ECOG performance status 0 or 1.
• Resolution of all acute toxic effects of prior therapy or surgical procedure to grade 1.

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 has 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 cannot be controlled by medications (>150/100 mm/Hg despite optimal medical therapy).
• Ongoing treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed).
• Known human immunodeficiency virus (HIV) infection.
• Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment.