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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00336063
First received: June 8, 2006
Last updated: July 18, 2014
Last verified: June 2014

June 8, 2006
July 18, 2014
March 2006
May 2015   (final data collection date for primary outcome measure)
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 ]
Not Provided
Complete list of historical versions of study NCT00336063 on ClinicalTrials.gov Archive Site
  • 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.
Not Provided
Not Provided
Not Provided
 
Vorinostat and Azacitidine in Treating Patients With Locally Recurrent or Metastatic Nasopharyngeal Cancer or Nasal Natural Killer T-Cell Lymphoma
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 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.

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
  • Drug: azacitidine
    Given SC
    Other Names:
    • 5-AC
    • 5-azacytidine
    • azacytidine
    • Vidaza
  • Drug: vorinostat
    Given orally
    Other Names:
    • L-001079038
    • SAHA
    • suberoylanilide hydroxamic acid
    • Zolinza
  • Other: diagnostic laboratory biomarker analysis
    Correlative studies
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
  • Procedure: axillary lymph node biopsy
    Correlative studies
    Other Name: axillary node biopsy
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.
Interventions:
  • Drug: azacitidine
  • Drug: vorinostat
  • Other: diagnostic laboratory biomarker analysis
  • Other: pharmacological study
  • Procedure: axillary lymph node biopsy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
18
Not Provided
May 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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
  • 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
  • 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
Both
21 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   China,   Japan,   Singapore
 
NCT00336063
NCI-2009-00089, NCI-2009-00089, CDR0000472702, CTRG-NP03/19/04, NCI-6837, CTRG NP03/19/04, 6837
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Wen-Son Hsieh Johns Hopkins University
National Cancer Institute (NCI)
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP