A Phase II Study of Single Agent Depsipeptide (FK228; NSC 630176; IND 51,810) in Patients With Unresectable Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

PRIMARY OBJECTIVES: I. To evaluate the rate of disease control (i.e., achievement of complete response, partial response, or stable disease) of the single agent depsipeptide in patients with unresectable recurrent or metastatic squamous cell carcinoma of the head and neck. SECONDARY OBJECTIVES: I. To evaluate the duration of response, time to progression, and overall survival for patients with incurable head and neck cancer treated with depsipeptide. TERTIARY OBJECTIVES: I. To determine the extent of histone hyperacetylation in peripheral blood mononuclear cells (PBMCs) as a readout of depsipeptide activity before and after depsipeptide administration, to correlate this activity with observed histone hyperacetylation in tumor and mucosal cells, and to correlate extent of depsipeptide activity with tumor response. II. To determine depsipeptide-induced changes in the gene expression profile of tumor cells from biopsies of accessible tumor tissue and of mucosal cells from transepithelial oral brush biopsies using cDNA microarrays containing 28,000 clones, and to correlate these changes with extent of histone hyperacetylation observed in PBMCs and tumor tissues. III. To determine depsipeptide-induced changes in methylation of candidate genes in tumor cells and oral mucosa epithelia. IV. To demonstrate altered expression of signaling and cell cycle-related proteins in tumor tissue in response to depsipeptide. OUTLINE: This is a multicenter study. Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years.