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

July 31, 2019 updated by: University of California, San Diego

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093-0658
        • Rebecca and John Moores UCSD Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: Single Arm Study of Biopsy
Genetic: protein expression analysis
Procedure: biopsy
Genetic: polymerase chain reaction
Drug: oral sodium phenylbutyrate
Drug: valganciclovir

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Tumor response in patients with measurable disease as assessed by RECIST criteria

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Diego

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 1, 2006

Primary Completion (ACTUAL)

January 1, 2008

Study Completion (ACTUAL)

January 1, 2008

Study Registration Dates

First Submitted

October 12, 2006

First Submitted That Met QC Criteria

October 12, 2006

First Posted (ESTIMATE)

October 13, 2006

Study Record Updates

Last Update Posted (ACTUAL)

August 2, 2019

Last Update Submitted That Met QC Criteria

July 31, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCSD-050126
  • CDR0000504022 (REGISTRY: PDQ (Physician Data Query))
  • ROCHE-VAL-108

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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