Gene Therapy in Treating Patients With Primary Brain Tumors

March 12, 2019 updated by: Abramson Cancer Center of the University of Pennsylvania

A PHASE I TRIAL OF HSV-TK ADENOVIRUS GENE THERAPY FOR PRIMARY BRAIN TUMORS

RATIONALE: Inserting the gene for herpes virus into a person's cells may improve the body's ability to fight cancer or make the cancer more sensitive to chemotherapy using antiviral drugs such as ganciclovir.

PURPOSE: Phase I trial to study the effectivenesss of gene therapy in treating patients with primary brain tumors.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES: I. Assess the response to a stereotactically administered recombinant adenovirus vector carrying the herpes simplex virus thymidine kinase gene (H5.010RSVTK) followed by intravenous ganciclovir in patients with recurrent malignant glioma. II. Estimate the maximum tolerated dose of H5.010RSVTK in these patients. III. Describe the toxic effects of H5.010RSVTK. IV. Assess the efficiency of gene transfer and duration of transgene expression in these patients. V. Assess quantitative and qualitative glucose metabolic activity of tumoral sites by positron emission tomography. VI. Analyze the immunologic response to adenovirus transduction in these patients. VII. Determine the benefit and toxicity of multiple doses of H5.010RSVTK in patients with resectable tumors.

OUTLINE: This is a dose-finding study. All patients receive stereotactically injected H5.010RSVTK (a recombinant adenovirus vector containing the herpes simplex virus thymidine kinase gene). Cohorts of 3-6 patients receive escalating doses of H5.010RSVTK until the maximum tolerated dose is reached. Ganciclovir is then given on the third post-injection day. Patients with unresectable tumors receive ganciclovir for 14 consecutive days. Patients with resectable tumors receive ganciclovir for 7 consecutive days before undergoing craniotomy with optimal debulking and injection of a second dose of the adenovirus vector followed by ganciclovir for 14 more days. Patients are followed monthly for survival.

PROJECTED ACCRUAL: A total of 18 patients (9 with resectable tumors and 9 with unresectable tumors) will be entered over 3 years.

Study Type

Interventional

Phase

  • Phase 1

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
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania 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 to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS: Histologically confirmed malignant glioma, including: Anaplastic astrocytoma Glioblastoma Evidence of recurrence by MRI and positron emission tomography despite primary treatment that included radiotherapy with or without chemotherapy Stereotactically accessible tumor Solitary tumor preferred Largest tumor surgically accessible for debulking if multifocal disease Not adjacent to optic chiasm or brain stem No subependymal spread No herniation or marked midline shift Consent for autopsy required

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70%-100% Hematopoietic: Hematologic parameters normal Hepatic: Hepatic parameters normal (less than twice normal if on anticonvulsants) Renal: Renal parameters normal Cardiovascular: No congestive heart failure No angina Other: No medical contraindication to neurosurgery and fluid injection into brain No serious uncontrolled infection Negative pregnancy test required of fertile women prior to entry Adequate contraception required of fertile women during and for 3 months after treatment

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics At least 2 months since radiotherapy Surgery: Not specified

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

Collaborators and Investigators

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

Sponsor

Abramson Cancer Center of the University of Pennsylvania

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Jane B. Alavi, MD, Abramson Cancer Center of the University of Pennsylvania

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

February 1, 1996

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

July 28, 2004

First Posted (Estimate)

July 29, 2004

Study Record Updates

Last Update Posted (Actual)

March 13, 2019

Last Update Submitted That Met QC Criteria

March 12, 2019

Last Verified

July 1, 2000

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000065004
  • UPCC-3394
  • NCI-H96-0976

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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