| Inclusion Criteria: | 1) Histologically confirmed diagnosis of Kit expressing advanced GIST. This includes patients with metastatic disease or with primary tumors that are considered inoperable.
2) A pre-imatinib mesylate paraffin block of tumor or 20 unstained slides should be submitted for correlative studies, if available.
3) Patients may have "limited" (some but not all tumor foci progressing that are not amenable to local therapy) or "generalized" (widespread growth of all tumor foci) progression after adequate therapy with imatinib mesylate. Patients must have progression of disease on imatinib mesylate (at any dose greater than or equal to 300 milligrams daily).
4) Patients must have documented measurable disease by CT scan (>2 cm by conventional CT or > 1 cm by spiral CT). If a targeted lesion has been previously embolized or irradiated, there must be objective evidence of progression of the lesion per CT scan, post-embolization or in the radiated field.
5) ECOG performance status of 0 - 2.
6) Patients must be at least 18 years of age or older.
7) Patients must be at least four weeks out and recovered from effects of prior therapy, including radiation, embolization, biotherapy or chemotherapy (with the exception of imatinib mesylate or other tyrosine kinase inhibitors). There is no washout period for imatinib mesylate.
8) Adequate organ function defined as absolute neutrophil count greater than or equal to 1,000/mm3, hemoglobin greater than or equal to 9.0 g/dl, and platelets greater than or equal to 100,000/mm3.
9) Adequate organ function defined as: Serum creatinine less than or equal to 1.5 mg/dl x ULN, Total bilirubin less than or equal to 1.5 x ULN, SGOT or SGPT less than or equal to 2.5 x ULN if no liver metastases. If liver metastases present less than or equal to 5 x ULN.
10) Patients must be able to understand and sign written informed consent and comply with study requirements.
11) All patients must have progressive disease on imatinib defined as: An increase in unidimensional tumor size of >10% and did not meet criteria for PR by CT density; Any new lesions, including new tumor nodules in a previously cystic tumor, while on imatinib therapy.
12) Patients need not be on imatinib mesylate at the time of protocol registration if there is documented disease progression per RECIST while on imatinib therapy. Patients may have been treated post imatinib with other treatment modalities and still be eligible for this study. Patients will resume dose of imatinib mesylate taken at time of disease progression during treatment, or at the highest dose best tolerated while on pre-study imatinib therapy (must be at least 300 mg daily for at least 1 month). |