Sorafenib Tosylate in Treating Patients With Progressive Metastatic Neuroendocrine Tumors
Sorafenib Tosylate in Treating Patients With Progressive Metastatic Neuroendocrine Tumors
This phase II trial is studying how well sorafenib tosylate works in treating patients with
 progressive metastatic neuroendocrine tumors. Sorafenib tosylate may stop the growth of tumor
 cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to
 the tumor.
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