Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

FR901228 in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors

Basic Trial Information

Objectives

Primary

1. Determine objective response rate in patients with locally advanced or metastatic neuroendocrine tumors treated with FR901288 (depsipeptide).

Secondary

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

Entry 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

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 (depsipeptide)
• 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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 6 months

Hematopoietic

• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³

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

Expected Enrollment

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

Outline

Patients receive FR901228 (depsipeptide) 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.

Trial Contact Information

Trial Lead Organizations

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Manisha Shah, MD, Principal investigator		Ph: 614-293-8629 Email: manisha.shah@osumc.edu

Registry Information
Official Title		Phase II Study of Depsipeptide in Metastatic Neuroendocrine Tumors
Trial Start Date		2004-03-24
Registered in ClinicalTrials.gov		NCT00084461
Date Submitted to PDQ		2004-03-30
Information Last Verified		2004-11-22
NCI Grant/Contract Number		U01-CA76576, P30-CA16058

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