Phenylbutyrate and Valganciclovir in Treating Patients With Relapsed or Refractory Epstein-Barr Virus-Positive Cancer

Lymphoma Clinical Trial

Official title:

A Phase II Study of Phenylbutyrate and Valganciclovir in Epstein-Barr Virus Positive Tumors

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00387530
• Other study ID #: UCSD-050126
• Secondary ID: CDR0000504022ROC
• Status: Withdrawn
• Phase: Phase 2
• Start date: May 2006
• Est. completion date: January 2008

Study information

• Verified date: July 2019
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Gastric Cancer
• Head and Neck Cancer
• Head and Neck Neoplasms
• Lymphoma
• Lymphoproliferative Disorder
• Lymphoproliferative Disorders
• Stomach Neoplasms

Intervention

Drug:
• oral sodium phenylbutyrate

• valganciclovir

Genetic:
• polymerase chain reaction

• protein expression analysis

Procedure:
• biopsy

Locations

Country	Name	City	State
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Diego	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	Tumor response in patients with measurable disease as assessed by RECIST criteria