Vorinostat and Azacitidine in Treating Patients With Locally Recurrent or Metastatic Nasopharyngeal Cancer or Nasal Natural Killer T-Cell Lymphoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00336063|
Recruitment Status : Active, not recruiting
First Posted : June 12, 2006
Last Update Posted : March 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Adult Nasal Type Extranodal NK/T-Cell Lymphoma Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma Recurrent Nasopharyngeal Undifferentiated Carcinoma Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7 Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7||Drug: Azacitidine Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Vorinostat||Phase 1|
I. 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||March 3, 2006|
|Actual Primary Completion Date :||April 19, 2013|
Experimental: Treatment (azacitidine, vorinostat)
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.
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesOther: Pharmacological Study
Correlative studiesDrug: Vorinostat
- 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 ]Graded according to the National Cancer Institute/Division of Cancer Treatment Common Toxicity Criteria.
- Precision of the estimated dose-response curve based on induction of lytically replicated viral particles in the plasma following treatment [ Time Frame: Up to 16 weeks ]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.
- Pharmacokinetics of vorinostat in patients with locally recurrent and metastatic nasopharyngeal carcinoma and NK-T cell nasal lymphoma [ Time Frame: 0, 15, 45, 60, 120, 180, 270, 360, and 480 minutes on days 1 and 14 of course 1 ]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.
- Proportions of patients with high and low histone acetylation [ Time Frame: Baseline ]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.
- EBV promoter demethylation as measured in tumor patients with locally recurrent and metastatic nasopharyngeal carcinoma and NK-T cell nasal lymphoma [ Time Frame: Baseline ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00336063
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21287|
|China, Hong Kong|
|Chinese University of Hong Kong-Prince of Wales Hospital|
|Shatin, Hong Kong, China|
|National University Hospital Singapore|
|Singapore, Singapore, 119074|
|National Cancer Centre|
|Singapore, Singapore, 169610|
|Johns Hopkins Singapore|
|Singapore, Singapore, 308433|
|Principal Investigator:||Wen-Son Hsieh||Johns Hopkins Singapore|