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

Primary Purpose

Gastric Cancer, Head and Neck Cancer, Lymphoma

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
oral sodium phenylbutyrate
valganciclovir
polymerase chain reaction
protein expression analysis
biopsy
Sponsored by
University of California, San Diego
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Rebecca and John Moores UCSD Cancer Center

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Single Arm Study of Biopsy

Arm Description

Outcomes

Primary Outcome Measures

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

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

Full Information

First Posted
October 12, 2006
Last Updated
July 31, 2019
Sponsor
University of California, San Diego
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00387530
Brief Title
Phenylbutyrate and Valganciclovir in Treating Patients With Relapsed or Refractory Epstein-Barr Virus-Positive Cancer
Official Title
A Phase II Study of Phenylbutyrate and Valganciclovir in Epstein-Barr Virus Positive Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Withdrawn
Study Start Date
May 2006 (Actual)
Primary Completion Date
January 2008 (Actual)
Study Completion Date
January 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Diego
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer, Head and Neck Cancer, Lymphoma, Lymphoproliferative Disorder
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single Arm Study of Biopsy
Arm Type
Other
Intervention Type
Drug
Intervention Name(s)
oral sodium phenylbutyrate
Intervention Type
Drug
Intervention Name(s)
valganciclovir
Intervention Type
Genetic
Intervention Name(s)
polymerase chain reaction
Intervention Type
Genetic
Intervention Name(s)
protein expression analysis
Intervention Type
Procedure
Intervention Name(s)
biopsy
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Tumor response in patients with measurable disease as assessed by RECIST criteria

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William L. Read, MD
Organizational Affiliation
University of California, San Diego
Official's Role
Study Chair
Facility Information:
Facility Name
Rebecca and John Moores UCSD Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0658
Country
United States

12. IPD Sharing Statement

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

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