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

Sponsor:	Johns Hopkins University
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00336063

Purpose

RATIONALE: 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 or by stopping them from dividing. 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.

PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat when given together with azacitidine in treating patients with locally recurrent or metastatic nasopharyngeal cancer or nasal natural killer T-cell lymphoma.

Condition	Intervention	Phase
Head and Neck Cancer Lymphoma	Drug: azacitidine Drug: vorinostat Other: laboratory biomarker analysis Other: pharmacological study Procedure: biopsy	Phase I

Study Type:	Interventional
Study Design:	Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Head and Neck Cancer Lymphoma

Drug Information available for: Suberoylanilide hydroxamic acid Azacitidine

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Pharmacokinetics [ Designated as safety issue: No ]

Estimated Enrollment:	18
Study Start Date:	March 2006
Estimated Primary Completion Date:	August 2007 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

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.
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.

Secondary

Assess the effect of SAHA on histone acetylation as measured in tumor and peripheral blood mononuclear cells of these patients.
Assess the effect of azacitidine on EBV promoter demethylation in these patients.
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 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.

PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	21 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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 meningitis
- Skull base involvement allowed

PATIENT CHARACTERISTICS:

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 following:
- 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

PRIOR CONCURRENT THERAPY:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00336063

Locations

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Recruiting
Baltimore, Maryland, United States, 21231-2410
Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce 410-955-8804 jhcccro@jhmi.edu
China
Prince of Wales Hospital	Recruiting
Hong Kong, China
Contact: Anthony T.C. Chan, MD 852-2632-2144 anthonytcchan@cuhk.edu.hk
Singapore
Cancer Institute at National University Hospital	Recruiting
Singapore, Singapore, 119074
Contact: Boon C. Goh, MD 65-6772-4617
Johns Hopkins Singapore International Medical Centre	Recruiting
Singapore, Singapore, 119074
Contact: Wen-Son Hsieh 65-6871-8132
National Cancer Centre - Singapore	Recruiting
Singapore, Singapore, 169610
Contact: Eng H. Tan, MD 65-6-436-8171 dmoteh@nccs.com.sg

Sponsors and Collaborators

Johns Hopkins University

National Cancer Institute (NCI)

Investigators

Study Chair:

Boon C. Goh, MD

Cancer Institute at National University Hospital

More Information

No publications provided

ClinicalTrials.gov Identifier:	NCT00336063 History of Changes
Other Study ID Numbers:	CDR0000472702, CTRG-NP03/19/04, NCI-6837
Study First Received:	June 8, 2006
Last Updated:	March 8, 2011
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Head and Neck Neoplasms
Lymphoma
Lymphoma, T-Cell
Nasopharyngeal Neoplasms
Neoplasms by Site
Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms

Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Azacitidine
Vorinostat
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Histone Deacetylase Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012