Vorinostat and Azacitidine in Treating Patients With Locally Recurrent or Metastatic Nasopharyngeal Cancer or Nasal Natural Killer T-Cell Lymphoma

PRIMARY OBJECTIVES:

I. Define toxicity profile of escalating doses of suberoylanilide hydroxamic acid (SAHA)
given in conjunction with a fixed dose of 5 Azacytidine (5AC) (azacitidine) in patients with
locally recurrent and metastatic nasopharyngeal carcinoma and natural killer (NK)-T cell
nasal lymphoma.

II. Define the biologically optimal dose of SAHA given in conjunction with a fixed dose of
5AC in patients with locally recurrent and metastatic nasopharyngeal carcinoma and NKT cell
nasal lymphoma based on evidence of Epstein-Barr virus (EBV) lytic induction in tumor
biopsies and plasma.

III. Study the effect of 5AC on the pharmacokinetic of SAHA in patients with locally
recurrent and metastatic nasopharyngeal carcinoma and NK-T cell nasal lymphoma.

IV. Assess the effect of SAHA on histone acetylation as measured in tumor and peripheral
blood mononuclear cells of patients with locally recurrent and metastatic nasopharyngeal
carcinoma and NK-T cell nasal lymphoma V. Assess the effect of 5AC on EBV promoter
demethylation as measured in tumor patients with locally recurrent and metastatic
nasopharyngeal carcinoma and NK-T cell nasal lymphoma.

OUTLINE: This is a dose-escalation study of vorinostat (SAHA).

Patients receive azacitidine subcutaneously (SC) on days 1-10 and vorinostat orally (PO)
twice daily (BID) 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.

Inclusion Criteria:

- Biopsy proven nasopharyngeal carcinoma (World Health Organization [WHO] type 3) or
extranodal NK-T-cell non-Hodgkin's lymphoma, nasal type (recurrence or metastases does
not require tissue documentation)

- Patients must have metastatic disease or locally recurrent disease that is not
amendable to surgical resection

- Patients must have locally recurrent disease that is not amendable to further
treatment with radiotherapy with curative intent

- Patients must have metastatic disease or locally recurrent disease that has been
treated with at least one regimen of chemotherapeutic agents after relapse; patient
must be at least 4 weeks since prior chemotherapy or radiation therapy

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

- Life expectancy greater than 6 months

- Leukocytes >= 3,000/ul

- Absolute neutrophil count >= 1,500/ul

- Platelets >= 100,000/ul

- Total bilirubin =< 1.5 X normal institutional limits

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 X institutional upper limit of normal

- Prothrombin time =< 1.5 X normal institutional limits

- Serum albumin >= 2.7 grams/deciliter

- Creatinine =< 1.5 X normal institutional limits or a calculated creatinine clearance
of > 50 mls/min

- Sexually active women of child-bearing potential should have a negative serum or urine
pregnancy test within 21 days of enrolling on trial; women of child-bearing potential
and men must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry and for the duration of study participation;
should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician immediately

- Patients must be informed of the investigational nature of the treatment, results that
might be expected, and potential toxicities; they must be able to give informed
written consent according to federal and institutional guidelines

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier

- Patients may not be receiving any other investigational agents

- Patients with known central nervous system (CNS) involvement (brain metastases or
carcinomatous meningitis should be excluded from this clinical trial; patients with
skull base involvement are eligible for this study

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to 5AC or SAHA

- Patients should not have taken sodium valproate for at least 2 weeks prior to
enrollment

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with 5AC and SAHA

- Human immunodeficiency virus (HIV)-positive patients receiving combination
anti-retroviral therapy are excluded from the study

- Patients with chronic active hepatitis B are excluded from the study