RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase II trial is studying how well gefitinib works in treating patients with progressive metastatic neuroendocrine tumors.

Condition	Treatment or Intervention	Phase
Gastrinoma gastrointestinal carcinoid tumor Insulinoma Islet Cell Carcinoma metastatic gastrointestinal carcinoid tumor miscellaneous islet cell cancer	Drug: gefitinib  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the 6-month progression-free survival rate in patients with progressive metastatic neuroendocrine tumors treated with gefitinib.

Secondary

• Determine the objective tumor response rate in patients treated with this drug.
• Determine time to progression and progression-free and overall survival in 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 disease type (carcinoid vs islet cell and other neuroendocrine tumors).

Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 34-90 patients (22-51 for carcinoid stratum and 12-39 for islet cell/other neuroendocrine tumor stratum) will be accrued for this study within 9 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic neuroendocrine neoplasm OR primary neuroendocrine tumor with clear clinical evidence of metastases
• No anaplastic or high-grade histology
• Measurable disease
• Radiographic evidence of disease progression within the past 60 weeks after prior systemic therapy, chemoembolization, embolization, or observation and defined as 1 of the following:
• Appearance of a new lesion
• At least 20% increase in the longest diameter (LD) of any previously documented lesion OR an increase in the sum of the LDs of multiple lesions in aggregate of 20%
• No thyroid carcinoma of any histology 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 at least 1,000/mm^3
• Platelet count at least 75,000/mm^3
• Hemoglobin at least 8.0 g/dL

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 3 times ULN*
• AST no greater than 3 times ULN* NOTE: *5 times ULN if liver metastases are present

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No symptoms of congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Gastrointestinal

• No gastrointestinal tract disease resulting in an inability to take oral medication (e.g., dysphagia or inability to swallow capsules intact)
• No requirement for IV alimentation
• No active peptic ulcer disease

Ophthalmic

• No known abnormality of the cornea, such as any of the following:
• History of dry eye syndrome or Sjögren's syndrome
• Congenital abnormality
• Abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-rose)
• Abnormal corneal sensitivity test (e.g., Schirmer test)

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 uncontrolled illness
• 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

PRIOR CONCURRENT THERAPY: Biologic therapy

• At least 4 weeks since prior interferon injection

Chemotherapy

• At least 4 weeks since prior chemotherapy
• No more than 1 prior systemic chemotherapy regimen
• Chemoembolization is not considered systemic chemotherapy
• No concurrent chemotherapy

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 at least 1 month and there is documented tumor progression on the current dose with no plan for increasing the dose

Radiotherapy

• At least 3 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• At least 4 weeks since prior major surgery

Other

• Recovered from prior therapy
• At least 4 weeks since other prior systemic therapy
• At least 4 weeks since prior hepatic artery embolization/chemoembolization
• More than 7 days since prior administration of the following CYP3A4 inducers:
• Phenytoin
• Carbamazepine
• Barbiturates
• Rifampin
• Oxcarbazepine
• Rifapentine
• Modafinil
• Hypericum perforatum (St. John's wort)
• No prior procedures adversely affecting intestinal absorption
• No prior epidermal growth factor-targeted regimens (e.g., erlotinib, EKB-569, or gefitinib)
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational treatment
• No concurrent CYP3A4 inducers

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,  United States; Recruiting

Study chairs or principal investigators

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

Study ID Numbers:  CDR0000346420; MAYO-MC0279; NCI-6113; NCT00075439
Record last reviewed:  December 2004
Last Updated:  April 4, 2005
Record first received:  January 9, 2004
ClinicalTrials.gov Identifier:  NCT00075439
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08