Sorafenib in Treating Patients With Malignant Gastrointestinal Stromal Tumor That Progressed During or After Previous Treatment With Imatinib Mesylate and Sunitinib Malate

PRIMARY OBJECTIVES:

I. To determine the objective response rate of patients with imatinib and sunitinib-resistant malignant gastrointestinal stromal tumor who are treated with BAY 43-9006.

SECONDARY OBJECTIVES:

I. To determine the toxicity experienced by patients with imatinib and sunitinib -resistant malignant gastrointestinal stromal tumor who are treated with BAY 43-9006.

II. To determine progression-free survival and overall survival in patients with imatinib and sunitinib -resistant malignant gastrointestinal stromal tumor who are treated with BAY 43-9006.

TERTIARY OBJECTIVES:

I. To examine if mutational status of KIT and PDGFA in patients with imatinib- and sunitinib resistant malignant gastrointestinal stromal tumor correlate with response to BAY 43-9006.

OUTLINE: This is a multicenter study. Patients are stratified according to response to prior treatment with imatinib mesylate and sunitinib malate (imatinib mesylate- and sunitinib malate-responsive disease vs primary imatinib mesylate- and sunitinib malate-refractory disease).

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.

Inclusion criteria

• Histologically confirmed gastrointestinal stromal tumor

• Not amenable to curative surgery
• Kit-expressing tumor
• Disease progression (i.e., new lesion or 20% increase in unidimensional tumor size) on or after treatment with imatinib mesylate and sunitinib malate
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 20 mm by conventional techniques OR > 10 mm by spiral CT scan

• Only site of measurable disease must be outside of previously irradiated area
• No known brain metastases
• Performance status - ECOG 0-2
• More than 3 months
• Absolute neutrophil count > 1,500/mm^3
• Platelet count > 100,000/mm^3
• Bilirubin normal
• AST and ALT < 2.5 times upper limit of normal
• Creatinine ≤ 1.5 mg/dL
• Creatinine clearance > 60 mL/min
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No uncontrolled hypertension
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to sorafenib
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness
• No evidence of bowel perforation or obstruction
• No prior angiogenesis inhibitors
• No immunotherapy after the last dose of imatinib mesylate or sunitinib malate
• No chemotherapy or chemoembolization therapy after the last dose of imatinib mesylate or sunitinib malate
• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered
• At least 14 days since prior imatinib mesylate or sunitinib malate
• No prior sorafenib
• No prior inhibitors of MAPK-signaling intermediates
• No other investigational agent after the last dose of imatinib mesylate or sunitinib malate
• Concurrent anticoagulation therapy with warfarin allowed provided the following criteria are met:

• On a therapeutic stable warfarin dose
• INR ≤3
• No active bleeding or pathologic condition that confers a high risk of bleeding
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent administration of any of the following:

• Enzyme-inducing antiepileptic drugs (e.g., carbamazepine, phenytoin, or phenobarbital)
• Hypericum perforatum (St. John's wort)
• Rifampin
• No other concurrent anticancer agents or therapies