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AzTrials

Adult Nasal Type Extranodal NK/T-Cell LymphomaPhase 1NCT00336063

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

A Phase 1 study testing Azacitidine, Laboratory Biomarker Analysis and Pharmacological Study in people with Adult Nasal Type Extranodal NK/T-Cell Lymphoma and Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 5 sites in 4 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 21 years and older
What is being tested?
Azacitidine, Laboratory Biomarker Analysis and Pharmacological Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
5 sitesin 4 countries
Study dates
3 Mar 2006to 31 Mar 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

5 sites in 4 countries.

5 sites in 4 countries

Singapore2 sites

  • National University Hospital Singapore

    Singapore, 119074

  • National Cancer Centre Singapore

    Singapore, 168583

Other trials in Singapore

United States1 site

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

Other trials in United States

Hong Kong1 site

  • Chinese University of Hong Kong-Prince of Wales Hospital

    Shatin

Other trials in Hong Kong

Japan1 site

  • National Cancer Center Hospital

    Tokyo, 104 0045

Other trials in Japan

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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.

Being tested
Azacitidine, Laboratory Biomarker Analysis, Pharmacological Study, Vorinostat
Medical subject headings
Lymphoma, Extranodal NK-T-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AzacitidineDrug

    Also called 5 AZC, 5-AC, 5-Azacitidine, 5-Azacytidine

    Given SC

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • VorinostatDrug

    Also called L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid

    Given PO

Study groups in NCT00336063
Study groupRoleWhat they receive
Treatment (azacitidine, vorinostat)ExperimentalPatients 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.
Receives: Drug: Azacitidine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Vorinostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Day 28

  2. 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.

    Measured: Up to 16 weeks

Secondary outcomes (3)

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

    Performed using a validated high performance liquid chromatography method. Maximum concentration (Cmax) and time to Cmax will be read off the curve, terminal T1/2 will be derived using the slope of the terminal portion of the semilogarithmic concentration-time plot, incorporating at least 3 time points in the extrapolation of the curve. Area-under-the curve (AUC) (infinity) of the semilog plot will be estimated using the trapezoidal method, and oral clearance (CL/F) will be derived using Dose/AUC, volume of distribution will be calculated.

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

  2. Proportions of patients with high and low histone acetylation

    The proportion of patients whose histone acetylation status changes in each group will be estimated with its 95% confidence interval. Percent agreement and kappa will be used.

    Measured: Baseline

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

    The proportion of patients whose EBV promoter demethylation status changes in each group will be estimated with its 95% confidence interval. Percent agreement and kappa will be used.

    Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jun 2006 (estimated)
  2. Study start3 Mar 2006
  3. Primary completion19 Apr 2013
  4. Study completion31 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00336063
Sponsor's protocol ID
NCI-2009-00089
Other IDs
NCI-2009-00089, NCI-6837, CTRG NP03/19/04, CDR0000472702, CTRG NP03/19/04, 6837, P30CA006973
Status last verified
Aug 2026
First submitted
8 Jun 2006
Last updated
19 Aug 2026
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Azacitidine, Laboratory Biomarker Analysis and Pharmacological Study in people with Adult Nasal Type Extranodal NK/T-Cell Lymphoma and Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 5 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Singapore, United States, Hong Kong, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: Day 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00336063.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2026.

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