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