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

NCT00336063 | Active Not Recruiting Phase 1

• 6 other identifiers: NCI-2009-00089NCI-6837CTRG NP03/19/04CDR00004727026837P30CA006973
• Study Type: interventional
• Target: 18
• Locations: 4 countries
• Sites: 5

Brief Summary

This phase I trial studies the side effects and best dose of vorinostat when given together with azacitidine in treating patients with nasopharyngeal cancer or nasal natural killer T-cell lymphoma that has recurred (come back) at or near the same place as the original (primary) tumor, usually after a period of time during which the cancer could not be detected or has spread to other parts of the body. Drugs used in chemotherapy, such as vorinostat and azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Vorinostat and azacitidine also may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving vorinostat together with azacitidine may kill more cancer cells.

Conditions

Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Nasopharyngeal Undifferentiated Carcinoma; Adult Nasal Type Extranodal NK/T-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of vorinostat and azacitidine, defined as the dose at which less than one-third of patients experience a dose limiting toxicity (i.e., fewer than 2 of 6 patients)

  Graded according to the National Cancer Institute/Division of Cancer Treatment Common Toxicity Criteria.

  Day 28

• Precision of the estimated dose-response curve based on induction of lytically replicated viral particles in the plasma following treatment

  A non-parametric and a parametric approach will be used. The non-parametric approach will entail averaging the biologic effects from the patients at each time point, plotting them versus dose, and connecting the points to get the dose-response curve. The parametric approach will use a polynomial regression model with two degrees of freedom for modeling dose. A spline model may also be used.

  Up to 16 weeks

Secondary Outcomes (3)

• Pharmacokinetics of vorinostat in patients with locally recurrent and metastatic nasopharyngeal carcinoma and NK-T cell nasal lymphoma

  0, 15, 45, 60, 120, 180, 270, 360, and 480 minutes on days 1 and 14 of course 1

• Proportions of patients with high and low histone acetylation

  Baseline

• EBV promoter demethylation as measured in tumor patients with locally recurrent and metastatic nasopharyngeal carcinoma and NK-T cell nasal lymphoma

  Baseline

Study Arms (1)

Treatment (azacitidine, vorinostat)

EXPERIMENTAL

Patients receive azacitidine SC on days 1-10 and vorinostat PO BID on days 1-14. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Drug: Azacitidine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Vorinostat

Interventions

Azacitidine DRUG

Given SC

Also known as: 5 AZC, 5-AC, 5-Azacitidine, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Treatment (azacitidine, vorinostat)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (azacitidine, vorinostat)

Pharmacological Study OTHER

Correlative studies

Treatment (azacitidine, vorinostat)

Vorinostat DRUG

Given PO

Also known as: L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid, Zolinza

Treatment (azacitidine, vorinostat)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Chinese University of Hong Kong-Prince of Wales Hospital

Shatin, Hong Kong

Location

National Cancer Center Hospital

Tokyo, 104 0045, Japan

Location

National University Hospital Singapore

Singapore, 119074, Singapore

Location

National Cancer Centre Singapore

Singapore, 168583, Singapore

Location

MeSH Terms

Conditions

Lymphoma, Extranodal NK-T-Cell

Interventions

Azacitidine; Vorinostat

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Wen-Son Hsieh

  Johns Hopkins Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2006
• First Posted: June 12, 2006
• Study Start: March 3, 2006
• Primary Completion: April 19, 2013
• Study Completion (Estimated): March 31, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-02

Locations

HK (1); JP (1); US (1); SG (2)