Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

Romidepsin in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00084461
Recruitment Status : Terminated
First Posted : June 11, 2004
Last Update Posted : June 4, 2013
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Phase 2

Detailed Description:


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


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.


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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Depsipeptide in Metastatic Neuroendocrine Tumors
Study Start Date : March 2004
Actual Primary Completion Date : October 2004

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 Names:
  • FK228
  • FR901228
  • Istodax

Other: laboratory biomarker analysis
Correlative studies

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

Secondary Outcome Measures :
  1. Incidence of toxicity [ Time Frame: Up to 4 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00084461

Layout table for location information
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
National Cancer Institute (NCI)
Layout table for investigator information
Principal Investigator: Manisha Shah Ohio State University
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI) Identifier: NCT00084461    
Other Study ID Numbers: NCI-2012-01449
U01CA076576 ( U.S. NIH Grant/Contract )
First Posted: June 11, 2004    Key Record Dates
Last Update Posted: June 4, 2013
Last Verified: June 2013
Additional relevant MeSH terms:
Layout table for MeSH terms
Neuroendocrine Tumors
Carcinoid Tumor
Malignant Carcinoid Syndrome
Gastrointestinal Neoplasms
Carcinoma, Islet Cell
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms, Glandular and Epithelial
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Adenoma, Islet Cell
Pancreatic Neoplasms
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases
Carcinoma, Neuroendocrine
Antibiotics, Antineoplastic