A Phase I Trial of 5Azacitidine and Suberoylanilide Hydroxamic Acid in Patients With Metastatic or Locally Recurrent Nasopharyngeal Carcinoma and Nasal NK-T Cell Lymphoma
I. Determine the dose-limiting toxicity of vorinostat (SAHA) in combination with azacitidine
in patients with locally recurrent or metastatic nasopharyngeal carcinoma or nasal type
natural killer (NK)/T-cell lymphoma.
II. Determine the maximum tolerated dose of SAHA given in combination with a fixed dose
azacitidine in these patients, based on evidence of Epstein-Barr virus (EBV) lytic induction
in tumor biopsies and plasma.
I. Assess the effect of SAHA on histone acetylation as measured in tumor and peripheral
blood mononuclear cells of these patients.
II. Assess the effect of azacitidine on EBV promoter demethylation in these patients.
III. Study the effect of azacitidine on the pharmacokinetics of SAHA in these patients.
OUTLINE: This is a multicenter, dose-escalation study of vorinostat (SAHA).
Patients receive azacitidine subcutaneously (SC) on days 1-10 and oral SAHA twice daily on
days 1-14. Treatment repeats every 28 days for 4 courses in the absence of disease
progression or unacceptable toxicity.
Patients with responding disease may continue treatment at the discretion of the principal
investigator. Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
of 3 or 2 of 6 patients experience dose-limiting toxicity. Six patients are treated at the
MTD. Patients undergo blood collection periodically during study for pharmacologic and
biomarker correlative studies. Some patients also undergo tumor biopsies for biomarker
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of SAHA in conjunction with azacitidine defined as the dose at which less than one-third of patients experience a DLT Graded according to the National Cancer Institute (NCI)/Division of Cancer Treatment (DCT) common toxicity criteria
Johns Hopkins University
United States: Food and Drug Administration
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