A Phase II Study of Phenylbutyrate and Valganciclovir in Epstein-Barr Virus Positive Tumors
18 Years
N/A
Both
Gastric Cancer, Head and Neck Cancer, Lymphoma, Lymphoproliferative Disorder
Trial Information
A Phase II Study of Phenylbutyrate and Valganciclovir in Epstein-Barr Virus Positive Tumors
OBJECTIVES:
Primary
- Determine the rate of Epstein-Barr virus (EBV) lytic phase activation by BZLF1
expression in patients with relapsed or refractory, EBV-positive malignancies treated
with phenylbutyrate.
Secondary
- Determine tumor responses in patients treated with phenylbutyrate followed by
valganciclovir.
- Track serum EBV load by quantitative polymerase chain reaction and correlate changes
with EBV lytic phase activation/tumor response.
OUTLINE: This is an open-label study.
Patients receive oral phenylbutyrate three times daily on days 1-21 and oral valganciclovir
once or twice daily on days 4-21. Treatment repeats every 21 days for up to 2 years in the
absence of disease progression or unacceptable toxicity.
Patients undergo biopsy on day 3 of course 1. Serum Epstein-Barr virus DNA is analyzed for
expression of BZLF1 and LMP2 by quantitative polymerase chain reaction on days 3 and 14 of
course 1 and on day 1 of each subsequent course.
After completion of study treatment, patients are followed at 1 and 3 months.
PROJECTED ACCRUAL: A total of 14 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Biopsy-proven Epstein-Barr virus (EBV)-positive malignancy
- Must have tissue analysis to confirm EBV positivity
- Archival tissue ≤ 1 year old may be used
- Any of the following malignancies:
- WHO type II or III nasopharyngeal carcinoma
- Post-transplant lymphoproliferative disorder
- Nasal NK/T-cell lymphoma
- Hodgkin's lymphoma
- Lymphoepithelioma-variant gastric carcinoma
- AIDS-related lymphomas
- Patients with CNS non-Hodgkin's lymphoma must have tumor cells present in
the cerebrospinal fluid (and assessable with lumbar puncture)
- Relapsed or refractory disease
- Must have received and failed all prior potentially curative treatment for
disease
- Eligible only for salvage therapy
- Must have tumor tissue amenable for minimally invasive biopsy (e.g., fine-needle
aspiration or bone marrow biopsy)
- No brain tumors not amenable to biopsy
- CNS metastases allowed provided ≥ 2 weeks since prior radiotherapy
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy ≥ 3 months
- Absolute granulocyte count ≥ 500/mm³
- Platelet count ≥ 50,000/mm³
- Bilirubin ≤ 1.5 times upper limit of normal
- Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 40 mL/min
- Recovered from 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
- Able to take medication orally or by gastrostomy tube
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception prior to, during, and for 90 days
after completion of study treatment
- No uncontrolled grade 1 symptomatic diarrhea (i.e., > 3 stools/day)
- No concurrent serious medical or psychiatric illness that would preclude study
participation
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Concurrent cerebrospinal fluid drugs allowed
- No concurrent zidovudine for HIV-positive patients
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Evidence of Epstein-Barr virus (EBV) lytic phase activation (expression of EBV antigens BZLF1 and LMP2) as assessed by biopsy on day 3 of course 1
Safety Issue:
No
Principal Investigator
William L. Read, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of California, San Diego
Authority:
United States: Federal Government
Study ID:
CDR0000504022
NCT ID:
NCT00387530
Start Date:
May 2006
Completion Date:
Related Keywords:
- Gastric Cancer
- Head and Neck Cancer
- Lymphoma
- Lymphoproliferative Disorder
- recurrent lymphoepithelioma of the nasopharynx
- post-transplant lymphoproliferative disorder
- adult nasal type extranodal NK/T-cell lymphoma
- recurrent adult Hodgkin lymphoma
- AIDS-related peripheral/systemic lymphoma
- AIDS-related primary CNS lymphoma
- recurrent gastric cancer
- Head and Neck Neoplasms
- Lymphoma
- Lymphoproliferative Disorders
- Stomach Neoplasms
Name | Location |
|---|---|
| Rebecca and John Moores UCSD Cancer Center | La Jolla, California 92093-0658 |
