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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2008 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00387530
First received: October 12, 2006
Last updated: February 6, 2009
Last verified: March 2008
  Purpose

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.


Condition Intervention Phase
Gastric Cancer
Head and Neck Cancer
Lymphoma
Lymphoproliferative Disorder
Drug: oral sodium phenylbutyrate
Drug: valganciclovir
Genetic: polymerase chain reaction
Genetic: protein expression analysis
Procedure: biopsy
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Phenylbutyrate and Valganciclovir in Epstein-Barr Virus Positive Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor response in patients with measurable disease as assessed by RECIST criteria [ Designated as safety issue: No ]

Estimated Enrollment: 14
Study Start Date: May 2006
Estimated Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00387530

Locations
United States, California
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
Sponsors and Collaborators
University of California, San Diego
Investigators
Study Chair: William L. Read, MD University of California, San Diego
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00387530     History of Changes
Other Study ID Numbers: CDR0000504022, UCSD-050126, ROCHE-VAL-108
Study First Received: October 12, 2006
Last Updated: February 6, 2009
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Head and Neck Neoplasms
Lymphoma
Lymphoproliferative Disorders
Stomach Neoplasms
Neoplasms by Site
Neoplasms
Neoplasms by Histologic Type
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
4-phenylbutyric acid
Valganciclovir
Ganciclovir
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 27, 2014