Sorafenib Tosylate in Treating Patients With Progressive Metastatic Neuroendocrine Tumors

PRIMARY OBJECTIVES:

I. To determine the objective tumor response rate of BAY 43-9006 (sorafenib tosylate) in patients with advanced neuroendocrine tumors.

SECONDARY OBJECTIVES:

I. Adverse event rate(s). II. Progression free survival and time to progression. III. Improvement in circulating hormone levels. IV. Overall survival.

OUTLINE: This is a multicenter study. Patients are grouped into 2 separate analysis Groups according to tumor type (Group A: Carcinoid; Group B: Islet cell/other well-differentiated tumor). Each Group was independently evaluated for all study endpoints.

Patients receive oral sorafenib tosylate 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 every 3 months until disease progression and then every 6 months for up to 2 years from study entry.

Criteria:

• Histologically confirmed neuroendocrine tumor:

• Carcinoid tumor OR islet cell carcinoma/other well-differentiated tumor
• No anaplastic or high-grade histology
• Metastatic disease
• Measurable disease
• No thyroid carcinoma of any histology, thymoma, or pheochromocytoma/paraganglioma
• No known brain metastases
• Performance status:

• Eastern Cooperative Oncology Group (ECOG) 0-2
• Life expectancy:

• At least 24 weeks
• Hematopoietic:

• Absolute neutrophil count >= 1,500/mm3
• Platelet count >= 100,000/mm3
• No bleeding diathesis
• Hepatic:

• Bilirubin =< 2 times upper limit of normal (ULN)
• Aspartate aminotransferase (AST) =< 3 times ULN (5 times ULN if liver metastases are present)
• International normalized ratio (INR) normal
• PTT normal
• Renal:

• Creatinine =< 1.5 times ULN
• Cardiovascular:

No poorly controlled hypertension; No symptoms of congestive heart failure; No unstable angina pectoris; No cardiac arrhythmia

• Gastrointestinal:

• Able to swallow capsules intact
• No gastrointestinal tract disease resulting in an inability to take oral medication (e.g., dysphagia)
• No requirement for IV alimentation
• No active peptic ulcer disease
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other invasive malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No other uncontrolled illness
• At least 4 weeks since prior interferon
• No more than 1 prior systemic chemotherapy regimen:

Chemoembolization is not considered systemic chemotherapy

• At least 4 weeks since prior chemoembolization
• At least 3 weeks since prior radiotherapy
• No prior procedures adversely affecting intestinal absorption
• At least 4 weeks since prior hepatic artery embolization
• No other prior systemic therapy
• No other concurrent investigational treatment
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent enzyme-inducing anticonvulsants (e.g., carbamazepine, phenobarbital, or phenytoin)
• No concurrent rifampin
• No concurrent Hypericum perforatum (St. John's wort)
• Prior or concurrent octreotide for symptomatic treatment allowed
• No concurrent therapeutic anticoagulation:

Concurrent prophylactic anticoagulation (i.e., low dose warfarin) of venous or arterial access devices allowed provided requirements for INR or PTT are met

• At least 4 weeks since prior major surgery
• Recovered from all prior therapy