Romidepsin in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors

Inclusion Criteria:

• 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
• Performance status - ECOG 0-1
• At least 6 months
• WBC >= 3,000/mm^3
• Absolute neutrophil count >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Bilirubin =< 1.5 mg/dL
• AST and ALT =< 2.5 times upper limit of normal
• Creatinine =< 1.5 mg/dL
• 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
• 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
• More than 4 weeks since prior immunotherapy (e.g., interferon alfa)
• 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)
• 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)
• More than 4 weeks since prior radiotherapy
• 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