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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

Phase 1
21 Years
Open (Enrolling)
Adult Nasal Type Extranodal NK/T-cell Lymphoma, Recurrent Lymphoepithelioma of the Nasopharynx, Recurrent Squamous Cell Carcinoma of the Nasopharynx, Stage IV Lymphoepithelioma of the Nasopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx

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Trial Information

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
correlative studies.

Inclusion Criteria:

- Biopsy proven nasopharyngeal carcinoma (WHO type 3) or extranodal nasal type natural
killer (NK)/T-cell non-Hodgkin's lymphoma

- Recurrence or metastases does not require tissue documentation

- Meets 1 of the following staging criteria:

- Locally recurrent disease

- Treated with ≥ 1 chemotherapy regimen after relapse

- Not amenable to surgical resection

- Not amenable to further curative radiotherapy

- Metastatic disease

- No clinical evidence of CNS involvement, including brain metastases or carcinomatous

- Skull base involvement allowed

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Life expectancy > 6 months

- WBC ≥ 3,000/mm³

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST/ALT ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)

- PTT ≤ 1.5 times ULN

- Albumin ≥ 2.7 g/dL

- Creatinine ≤ 1.5 times ULN OR creatinine clearance > 50 mL/min

- No uncontrolled intercurrent illness including, but not limited to, any of the

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situations that would limit study compliance

- Not pregnant or nursing

- Fertile patients must use effective contraception

- Negative pregnancy test

- No history of allergic reaction to compounds of similar chemical or biologic
composition to azacitidine or vorinostat (SAHA)

- No chronic active hepatitis B

- See Disease Characteristics

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
or radiotherapy and recovered

- At least 2 weeks since prior valproic acid

- No more than 1 concurrent multivitamin daily

- No concurrent prophylactic hematopoietic growth factors

- No other concurrent investigational agents

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent anticancer agents or therapies

- No other concurrent chemotherapy (including photopheresis), psoralen-ultraviolet
treatment (PUVA), radiotherapy, or biologic therapy

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

Day 28

Safety Issue:


Principal Investigator

Wen-Son Hsieh

Investigator Role:

Principal Investigator

Investigator Affiliation:

Johns Hopkins University


United States: Food and Drug Administration

Study ID:




Start Date:

March 2006

Completion Date:

Related Keywords:

  • Adult Nasal Type Extranodal NK/T-cell Lymphoma
  • Recurrent Lymphoepithelioma of the Nasopharynx
  • Recurrent Squamous Cell Carcinoma of the Nasopharynx
  • Stage IV Lymphoepithelioma of the Nasopharynx
  • Stage IV Squamous Cell Carcinoma of the Nasopharynx
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Lymphoma
  • Lymphoma, T-Cell
  • Nasopharyngeal Neoplasms
  • Lymphoma, Extranodal NK-T-Cell



Johns Hopkins University Baltimore, Maryland  21205