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

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

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

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

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).