Romidepsin In Treating Patients With Locally Advanced Or Metastatic Neuroendocrine Tumors

Study Overview

Romidepsin in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors

Phase II trial to study the effectiveness of romidepsin in treating patients who have locally advanced or metastatic neuroendocrine tumors. Drugs used in chemotherapy, such as romidepsin, work in different ways to stop tumor cells from dividing so they stop growing or die.

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.

Gastrinoma
Glucagonoma
Insulinoma
Metastatic Gastrointestinal Carcinoid Tumor
Pancreatic Polypeptide Tumor
Pulmonary Carcinoid Tumor
Recurrent Gastrointestinal Carcinoid Tumor
Recurrent Islet Cell Carcinoma
Regional Gastrointestinal Carcinoid Tumor
Somatostatinoma

DRUG: romidepsin
OTHER: laboratory biomarker analysis

NCI-2012-01449
0425
NCI-6325
OSU-2003C0085
CDR0000365313
U01CA076576 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2004-06-10	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2013-06-03
First Submitted that Met QC Criteria 2004-06-10	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2013-06-04
First Posted (ESTIMATED) 2004-06-11	Results First Posted N/A	Last Verified 2013-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (romidepsin) 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 CR receive 2 additional courses beyond CR.	DRUG: romidepsin Given IV OTHER: laboratory biomarker analysis Correlative studies

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (romidepsin)

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 CR receive 2 additional courses beyond CR.

DRUG: romidepsin

Given IV

OTHER: laboratory biomarker analysis

Correlative studies

Primary Outcome Measures	Measure Description	Time Frame
Objective response rate	Frequency of response will be estimated with a 95% confidence interval.	Up to 4 weeks

Secondary Outcome Measures	Measure Description	Time Frame
Incidence of toxicity		Up to 4 weeks

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Manisha Shah, Ohio State University

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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Resources

Patients

Caregivers

Clinical Trial Record