Vorinostat and Azacitidine in Treating Patients With Locally Recurrent or Metastatic Nasopharyngeal Cancer or Nasal Natural Killer T-Cell Lymphoma
Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: 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; Stage IV Nasopharyngeal Undifferentiated Carcinoma
Intervention: Azacitidine (Drug); Laboratory Biomarker Analysis (Other); Pharmacological Study (Other); Vorinostat (Drug)
Phase: Phase 1
Status: Active, not recruiting
Sponsored by: National Cancer Institute (NCI) Official(s) and/or principal investigator(s): Wen-Son Hsieh, Principal Investigator, Affiliation: Johns Hopkins Singapore
Summary
This phase I trial studies the side effects and best dose of vorinostat when given together
with azacitidine in treating patients with nasopharyngeal cancer or nasal natural killer
T-cell lymphoma that has recurred (come back) at or near the same place as the original
(primary) tumor, usually after a period of time during which the cancer could not be
detected or has spread to other parts of the body. 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, by stopping them from dividing, or by stopping them from
spreading. 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.
Clinical Details
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
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: 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)Precision of the estimated dose-response curve based on induction of lytically replicated viral particles in the plasma following treatment
Secondary outcome: EBV promoter demethylation as measured in tumor patients with locally recurrent and metastatic nasopharyngeal carcinoma and NK-T cell nasal lymphomaPharmacokinetics of vorinostat in patients with locally recurrent and metastatic nasopharyngeal carcinoma and NK-T cell nasal lymphoma Proportions of patients with high and low histone acetylation
Detailed description:
PRIMARY OBJECTIVES:
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.
Eligibility
Minimum age: 21 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Biopsy proven nasopharyngeal carcinoma (World Health Organization [WHO] type 3) or
extranodal NK-T-cell non-Hodgkin's lymphoma, nasal type (recurrence or metastases
does not require tissue documentation)
- Patients must have metastatic disease or locally recurrent disease that is not
amendable to surgical resection
- Patients must have locally recurrent disease that is not amendable to further
treatment with radiotherapy with curative intent
- Patients must have metastatic disease or locally recurrent disease that has been
treated with at least one regimen of chemotherapeutic agents after relapse; patient
must be at least 4 weeks since prior chemotherapy or radiation therapy
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Life expectancy greater than 6 months
- Leukocytes >= 3,000/ul
- Absolute neutrophil count >= 1,500/ul
- Platelets >= 100,000/ul
- Total bilirubin =< 1. 5 X normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2. 5 X institutional upper limit of normal
- Prothrombin time =< 1. 5 X normal institutional limits
- Serum albumin >= 2. 7 grams/deciliter
- Creatinine =< 1. 5 X normal institutional limits or a calculated creatinine clearance
of > 50 mls/min
- Sexually active women of child-bearing potential should have a negative serum or
urine pregnancy test within 21 days of enrolling on trial; women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence) prior to study entry and for the duration of
study participation; should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately
- Patients must be informed of the investigational nature of the treatment, results
that might be expected, and potential toxicities; they must be able to give informed
written consent according to federal and institutional guidelines
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- Patients with known central nervous system (CNS) involvement (brain metastases or
carcinomatous meningitis should be excluded from this clinical trial; patients with
skull base involvement are eligible for this study
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to 5AC or SAHA
- Patients should not have taken sodium valproate for at least 2 weeks prior to
enrollment
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with 5AC and SAHA
- Human immunodeficiency virus (HIV)-positive patients receiving combination
anti-retroviral therapy are excluded from the study
- Patients with chronic active hepatitis B are excluded from the study
Locations and Contacts
Johns Hopkins Singapore, Singapore 308433, Singapore
National Cancer Centre, Singapore 169610, Singapore
National University Hospital Singapore, Singapore 119074, Singapore
Chinese University of Hong Kong-Prince of Wales Hospital, Shatin, Hong Kong OX1 3UJ, China
Johns Hopkins University/Sidney Kimmel Cancer Center, Baltimore, Maryland 21287, United States
Additional Information
Starting date: March 2006
Last updated: July 16, 2015
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