Romidepsin in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00084461
First received: June 10, 2004
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Depsipeptide in Metastatic Neuroendocrine Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response rate [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
    Frequency of response will be estimated with a 95% confidence interval.


Secondary Outcome Measures:
  • Incidence of toxicity [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 25
Study Start Date: March 2004
Primary Completion Date: October 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00084461

Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Investigators
Principal Investigator: Manisha Shah Ohio State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00084461     History of Changes
Other Study ID Numbers: NCI-2012-01449, 0425, NCI-6325, OSU-2003C0085, CDR0000365313, U01CA076576
Study First Received: June 10, 2004
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neuroendocrine Tumors
Carcinoid Tumor
Malignant Carcinoid Syndrome
Gastrointestinal Neoplasms
Neoplasms
Carcinoma, Islet Cell
Insulinoma
Gastrinoma
Somatostatinoma
Glucagonoma
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Pancreatic Neoplasms
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases
Adenoma, Islet Cell
Adenoma
Carcinoma, Neuroendocrine
Romidepsin
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on September 16, 2014