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Phase II Study of Depsipeptide in Metastatic Neuroendocrine Tumors

Phase 2
18 Years
Not Enrolling
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

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Trial Information

Phase II Study of Depsipeptide in Metastatic Neuroendocrine Tumors


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.

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

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response rate

Outcome Description:

Frequency of response will be estimated with a 95% confidence interval.

Outcome Time Frame:

Up to 4 weeks

Safety Issue:


Principal Investigator

Manisha Shah

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University


United States: Food and Drug Administration

Study ID:




Start Date:

March 2004

Completion Date:

Related Keywords:

  • 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
  • Carcinoid Tumor
  • Carcinoma
  • Gastrinoma
  • Zollinger-Ellison Syndrome
  • Glucagonoma
  • Insulinoma
  • Somatostatinoma
  • Neuroendocrine Tumors
  • Malignant Carcinoid Syndrome
  • Gastrointestinal Neoplasms
  • Carcinoma, Islet Cell



Ohio State University Medical Center Columbus, Ohio  43210