Vorinostat and Azacitidine in Treating Patients With Locally Recurrent or Metastatic Nasopharyngeal Cancer or Nasal Natural Killer T-Cell Lymphoma
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. 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.
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
Other: diagnostic laboratory biomarker analysis
Other: pharmacological study
Procedure: axillary lymph node biopsy
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
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|
- 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 [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]
- Pharmacokinetics of SAHA in patients with locally recurrent and metastatic nasopharyngeal carcinoma and NK-T cell Nasal Lymphoma [ Time Frame: Days 1 and 14 of course 1 ] [ Designated as safety issue: No ]Performed using a validated high performance liquid chromatography (HPLC) 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 (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.
- Proportions of patients with high and low histone acetylation [ Time Frame: Baseline ] [ Designated as safety issue: No ]Will be estimated with its 95% confidence interval.
|Study Start Date:||March 2006|
|Estimated Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (chemotherapy, enzyme inhibitor therapy)
Patients receive azacitidine 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.
Other Names:Drug: vorinostat
Other Names:Other: diagnostic laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studiesProcedure: axillary lymph node biopsy
Other Name: axillary node biopsy
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00336063
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center|
|Baltimore, Maryland, United States, 21287|
|China, Hong Kong|
|Chinese University of Hong Kong-Prince of Wales Hospital|
|Shatin, Hong Kong, China, OX1 3UJ|
|National Cancer Center Hospital|
|Tokyo, Japan, 104 0045|
|National Cancer Centre|
|Singapore, Singapore, 169610|
|National University Hospital|
|Singapore, Singapore, 119074|
|Principal Investigator:||Wen-Son Hsieh||Johns Hopkins University|