Phenylbutyrate and Valganciclovir in Treating Patients With Relapsed or Refractory Epstein-Barr Virus-Positive Cancer
This trial is active, not recruiting.
|Conditions||gastric cancer, head and neck cancer, lymphoma, lymphoproliferative disorder|
|Treatments||oral sodium phenylbutyrate, valganciclovir, polymerase chain reaction, protein expression analysis, biopsy|
|Sponsor||University of California, San Diego|
|Collaborator||National Cancer Institute (NCI)|
|Start date||May 2006|
|End date||January 2008|
|Trial size||14 participants|
|Trial identifier||NCT00387530, CDR0000504022, ROCHE-VAL-108, UCSD-050126|
RATIONALE: The Epstein-Barr virus can cause cancer and lymphoproliferative disorders. Valganciclovir is an antiviral drug that acts against the Epstein-Barr virus. Phenylbutyrate may make cells infected with Epstein-Barr virus more sensitive to valganciclovir. Giving phenylbutyrate together with valganciclovir may block the growth of Epstein-Barr virus-infected cells and kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving phenylbutyrate together with valganciclovir works in treating patients with relapsed or refractory Epstein-Barr virus-positive cancer.
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
Tumor response in patients with measurable disease as assessed by RECIST criteria
Male or female participants at least 18 years old.
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
|Official title||A Phase II Study of Phenylbutyrate and Valganciclovir in Epstein-Barr Virus Positive Tumors|
|Description||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.|
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