Romidepsin in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors

Insulinoma Clinical Trial

Official title:

Phase II Study of Depsipeptide in Metastatic Neuroendocrine Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00084461
• Other study ID #: NCI-2012-01449
• Secondary ID: 0425NCI-6325OSU-
• Status: Terminated
• Phase: Phase 2
• First received: June 10, 2004
• Last updated: June 3, 2013
• Start date: March 2004

Study information

• Verified date: June 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. primary completion date: October 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Carcinoid Tumor
• Carcinoma, Islet Cell
• Gastrinoma
• Gastrointestinal Neoplasms
• Glucagonoma
• Insulinoma
• Malignant Carcinoid Syndrome
• Metastatic Gastrointestinal Carcinoid Tumor
• Neoplasms
• Neuroendocrine Tumors
• Pancreatic Polypeptide Tumor
• Pulmonary Carcinoid Tumor
• Recurrent Gastrointestinal Carcinoid Tumor
• Recurrent Islet Cell Carcinoma
• Regional Gastrointestinal Carcinoid Tumor
• Somatostatinoma

Intervention

Drug:
• romidepsin
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Ohio State University Medical Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate	Frequency of response will be estimated with a 95% confidence interval.	Up to 4 weeks	No
Secondary	Incidence of toxicity		Up to 4 weeks	Yes