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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

June 10, 2004
June 3, 2013
March 2004
October 2004   (final data collection date for primary outcome measure)
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.
Not Provided
Complete list of historical versions of study NCT00084461 on ClinicalTrials.gov Archive Site
Incidence of toxicity [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
Not Provided
 
Romidepsin in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors
Phase II Study of Depsipeptide in 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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    Given IV
    Other Names:
    • FK228
    • FR901228
    • Istodax
  • Other: laboratory biomarker analysis
    Correlative studies
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.
Interventions:
  • Drug: romidepsin
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
25
Not Provided
October 2004   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00084461
NCI-2012-01449, 0425, NCI-6325, OSU-2003C0085, CDR0000365313, U01CA076576
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Manisha Shah Ohio State University
National Cancer Institute (NCI)
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP