• Objective response rate (partial and complete response) [ Designated as safety issue: No ]
  

• Overall survival [ Designated as safety issue: No ]
  
• Progression-free survival [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the objective response rate (partial and complete response) in patients with imatinib mesylate- and sunitinib malate-resistant malignant gastrointestinal stromal tumor treated with sorafenib.

Secondary

• Determine the toxicity of this drug in these patients.
• Determine the progression-free survival and overall survival of patients treated with this drug.

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.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-2

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count > 1,500/mm^3
• Platelet count > 100,000/mm^3

Hepatic

• Bilirubin normal
• AST and ALT < 2.5 times upper limit of normal

Renal

• Creatinine ≤ 1.5 mg/dL OR
• Creatinine clearance > 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No uncontrolled hypertension

Other

• 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior angiogenesis inhibitors
• No immunotherapy after the last dose of imatinib mesylate or sunitinib malate

Chemotherapy

• No chemotherapy or chemoembolization therapy after the last dose of imatinib mesylate or sunitinib malate

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered

Other

• 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