FR901228 in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors

Official Title: “Phase II Study of Depsipeptide in Metastatic Neuroendocrine Tumors”

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.

OBJECTIVES:

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

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 (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.

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

Intervention(s) in this Clinical Trial

• Drug: romidepsin

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 (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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Arthur G. James Cancer Hospital & Richard J. Solove Research Institute Other

Overall Clinical Trial Officials and Contacts

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

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00084461

Study ID Number: CDR0000365313

ClinicalTrials.gov Identifier: NCT00084461

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database