Phase II Study of Depsipeptide in Metastatic Neuroendocrine Tumors
romidepsin
+ laboratory biomarker analysis
Adenocarcinoma+28
+ Adenoma
+ Carcinoid Tumor
Treatment Study
Summary
Study start date: March 1, 2004
Actual date on which the first participant was enrolled.PRIMARY OBJECTIVES: I. Determine objective response rate in patients with locally advanced or metastatic neuroendocrine tumors treated with FR901288 (romidepsin). SECONDARY OBJECTIVES: I. Determine the toxicity of this drug in these patients. II. To measure serum tumor markers (pancreastatin, gastrin, pancreatic polypeptide, glucagon, substance-P, neurotensin, calcitonin, somatostatin, vasoactive intestinal peptide, gastrin releasing polypeptide, ACTH) depending on the tumor type pre-, during-, and post-treatment. III. To perform a nuclear medicine functional imaging scan (octreoscan) to evaluate the disease status pre-, during-, and post-treatment. IV. To perform histone acetylation assay in cytospins from peripheral blood mononuclear cells (PBMCs) to correlate with disease response and with immunologic parameters. V. To quantify gene expression by Real Time PCR of type 1 and type 2 cytokines, co-stimulatory molecules, and adhesion molecules in PBMCs obtained from the pre-, during-, and post-treatment blood samples. VI. To perform a multicolor flow cytometric analysis on fresh blood to assess activation of lymphocyte subsets and presence of co-stimulatory and adhesion molecules. VII. To perform in vitro functional assays for innate as well as antigen-specific T cell immune responses in PBMCs obtained from the pre-, during-, and post-treatment blood samples. OUTLINE: Patients receive romidepsin 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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.25 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
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
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.One single intervention group is designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalStudy Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location