Gene Therapy in Treating Patients With Primary Brain Tumors

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00002824
First received: November 1, 1999
Last updated: February 6, 2009
Last verified: July 2000
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Biological: gene therapy
Drug: chemotherapy
Drug: ganciclovir
Procedure: conventional surgery
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A PHASE I TRIAL OF HSV-TK ADENOVIRUS GENE THERAPY FOR PRIMARY BRAIN TUMORS

Resource links provided by NLM:


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

Study Start Date: February 1996
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00002824

Locations
United States, Pennsylvania
University of Pennsylvania Cancer Center
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Investigators
Study Chair: Jane B. Alavi, MD Abramson Cancer Center of the University of Pennsylvania
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00002824     History of Changes
Other Study ID Numbers: CDR0000065004, UPCC-3394, NCI-H96-0976
Study First Received: November 1, 1999
Last Updated: February 6, 2009
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent adult brain tumor
adult glioblastoma
adult anaplastic astrocytoma
adult giant cell glioblastoma
adult gliosarcoma

Additional relevant MeSH terms:
Brain Neoplasms
Central Nervous System Neoplasms
Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Neoplasms by Site
Nervous System Diseases

ClinicalTrials.gov processed this record on October 29, 2014