RATIONALE: Drugs used in chemotherapy, such as FR901228, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of FR901228 in treating patients who have locally advanced or metastatic neuroendocrine tumors.

Condition	Treatment or Intervention	Phase
gastrointestinal carcinoid tumor Islet Cell Carcinoma pulmonary carcinoid tumor	Drug: FR901228  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: non-specific immune-modulator therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine objective response rate in patients with locally advanced or metastatic neuroendocrine tumors treated with FR901288.

Secondary

• Determine the toxicity of this drug in these patients.
• Correlate histone acetylation assay results with disease response and immunologic parameters in patients treated with this drug.

OUTLINE: Patients receive FR901228 IV over 4 hours on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete remission (CR) receive 2 additional courses beyond CR.

Patients are followed at 2-4 weeks.

PROJECTED ACCRUAL: A total of 16-25 patients will be accrued for this study within 4-6 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed carcinoid tumor or islet cell neuroendocrine tumor
• Well- or moderately-differentiated tumor
• Metastatic and/or locally advanced disease
• Measurable disease
• Unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
• Lesions in a previously irradiated area are not considered measurable
• No truly non-measurable lesions, including the following:
• Bone lesions
• Leptomeningeal disease
• Ascites
• Pleural or pericardial effusion
• Lymphangitis cutis/pulmonis
• Abdominal masses not confirmed and followed by imaging
• Cystic lesions
• Ineligible for standard treatment

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 6 months

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal

Renal

• Creatinine ≤ 1.5 mg/dL

Cardiovascular

• No New York Heart Association class III or IV congestive heart failure
• No myocardial infarction within the past year
• No uncontrolled dysrhythmias
• No poorly controlled angina
• No serious ventricular arrhythmia, defined as ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row
• No left ventricular hypertrophy by EKG
• No other significant cardiac disease
• QTc < 500 msec
• LVEF > 40% by resting MUGA

Other

• No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drug
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other concurrent uncontrolled illness
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 4 weeks since prior immunotherapy (e.g., interferon alfa)

Chemotherapy

• More than 4 weeks since prior chemotherapy
• More than 12 weeks since prior hepatic artery chemoembolization unless liver lesions are not the only indicator lesions
• No prior FR901228
• No more than 1 prior systemic chemotherapy regimen for carcinoid or islet cell tumor (other than hepatic artery chemoembolization)

Endocrine therapy

• More than 4 weeks since prior oral or IV steroids (first 16 patients only)
• Concurrent long-acting octreotide allowed at standard doses if dose has been stable for the past 12 weeks
• Concurrent subcutaneous octreotide for breakthrough use for symptomatic relief allowed
• No concurrent systemic steroids (first 16 patients only)

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since prior radiotherapy

Surgery

• Not specified

Other

• More than 4 weeks since prior investigational tumor-specific therapy
• No other prior histone deacetylase inhibitors (e.g., valproic acid)
• No concurrent hydrochlorothiazide
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational or commercial agents or therapies for the malignancy

Ohio
      Arthur G. James Cancer Hospital at Ohio State University, Columbus,  Ohio,  43210-1240,  United States

Study chairs or principal investigators

Manisha H. Shah, MD,  Principal Investigator,  Arthur G. James Cancer Hospital & Richard J. Solove Research Institute   

Study ID Numbers:  CDR0000365313; OSU-2003C0085; NCI-6325; NCT00084461
Record last reviewed:  January 2005
Last Updated:  January 7, 2005
Record first received:  June 10, 2004
ClinicalTrials.gov Identifier:  NCT00084461
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08