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
  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. 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.


Condition Intervention Phase
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
Drug: vorinostat
Other: diagnostic laboratory biomarker analysis
Other: pharmacological study
Procedure: axillary lymph node biopsy
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 18
Study Start Date: March 2006
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

Detailed Description:

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
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
Japan
National Cancer Center Hospital
Tokyo, Japan, 104 0045
Singapore
National Cancer Centre
Singapore, Singapore, 169610
National University Hospital
Singapore, Singapore, 119074
Sponsors and Collaborators
Investigators
Principal Investigator: Wen-Son Hsieh Johns Hopkins University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00336063     History of Changes
Other Study ID Numbers: NCI-2009-00089, NCI-2009-00089, CDR0000472702, CTRG-NP03/19/04, NCI-6837, CTRG NP03/19/04, 6837
Study First Received: June 8, 2006
Last Updated: July 18, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Lymphoma
Lymphoma, T-Cell
Lymphoma, Extranodal NK-T-Cell
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Azacitidine
Vorinostat
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 20, 2014