A PHASE I TRIAL OF HSV-TK ADENOVIRUS GENE THERAPY FOR PRIMARY BRAIN TUMORS
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
A PHASE I TRIAL OF HSV-TK ADENOVIRUS GENE THERAPY FOR PRIMARY BRAIN TUMORS
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Jane B. Alavi, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Abramson Cancer Center of the University of Pennsylvania
Authority:
United States: Federal Government
Study ID:
CDR0000065004
NCT ID:
NCT00002824
Start Date:
February 1996
Completion Date:
Related Keywords:
- Brain and Central Nervous System Tumors
- recurrent adult brain tumor
- adult glioblastoma
- adult anaplastic astrocytoma
- adult giant cell glioblastoma
- adult gliosarcoma
- Brain Neoplasms
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| University of Pennsylvania Cancer Center | Philadelphia, Pennsylvania 19104 |
