RATIONALE: Sorafenib 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.

PURPOSE: This phase II trial is studying how well sorafenib works in treating patients with progressivemetastatic neuroendocrine tumors.

Condition	Intervention	Phase
Gastrinoma gastrointestinal carcinoid tumor Insulinoma Islet Cell Carcinoma metastatic gastrointestinal carcinoid tumor miscellaneous islet cell cancer	Drug: sorafenib  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy	Phase II

Further Study Details: 

OBJECTIVES:

Primary

• Determine the objective tumor response rate in patients with progressive metastatic neuroendocrine tumors treated with sorafenib.

Secondary

• Determine the adverse event rate in patients treated with this drug.
• Determine time to progression and progression-free and overall survival of patients treated with this drug.
• Determine improvement in circulating hormone levels in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor type (carcinoid vs islet cell/other well-differentiated tumor).

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 every 3 months until disease progression and then every 6 months for up to 2 years from study entry.

PROJECTED ACCRUAL: Approximately 38-90 patients (22-46 with carcinoid tumors and 12-39 with islet cell carcinoma/other well-differentiated tumors) will be accrued for this study within 3.2-7.5 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 24 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No bleeding diathesis

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST ≤ 3 times ULN (5 times ULN if liver metastases are present)
• 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

Other

• 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 4 weeks since prior interferon

Chemotherapy

• No prior chemotherapy
• Chemoembolization is not considered systemic chemotherapy
• At least 4 weeks since prior chemoembolization

Endocrine therapy

• At least 2 weeks since prior short-acting octreotide injection (6 weeks for long-acting injection)
• Concurrent octreotide allowed provided a stable dose has been administered for ≥ 1 month and there is documented tumor regression on the current dose with no plan for increasing the dose

Radiotherapy

• At least 3 weeks since prior radiotherapy

Surgery

• At least 4 weeks since prior major surgery
• No prior procedures adversely affecting intestinal absorption

Other

• Recovered from all prior therapy
• 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)
• 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

Please refer to this study by ClinicalTrials.gov identifier  NCT00131911

Arizona
      Mayo Clinic Scottsdale, Scottsdale,  Arizona,  85259,  United States; Recruiting
District of Columbia
      Howard University Cancer Center at Howard University Hospital, Washington,  District of Columbia,  20060,  United States; Recruiting
Florida
      Mayo Clinic - Jacksonville, Jacksonville,  Florida,  32224,  United States; Recruiting
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  United States; Recruiting
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States; Recruiting
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
Missouri
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-3236,  United States; Recruiting

Study chairs or principal investigators

Timothy Hobday, MD,  Study Chair,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000437792; MAYO-MC044H; NCI-7046
Last Updated:  August 18, 2005
Record first received:  August 16, 2005
ClinicalTrials.gov Identifier:  NCT00131911
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-08-23