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.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective response rate
Frequency of response will be estimated with a 95% confidence interval.
Up to 4 weeks
Ohio State University
United States: Food and Drug Administration
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