Gene Therapy in Treating Patients With Recurrent Malignant Gliomas

Study Overview
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Brief Summary
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RATIONALE: Inserting the gene for adenovirus p53 into a person's tumor may improve the body's ability to fight cancer. PURPOSE: Phase I trial to study the effectiveness of gene therapy in treating patients who have recurrent malignant gliomas.

Detailed Description
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OBJECTIVES: I. Determine the biological effects at the molecular level of intratumoral administration of adenovirus p53 gene (Ad-p53) in patients with malignant primary glioma. II. Determine the maximum tolerated dose of intratumoral Ad-p53 in these patients. III. Evaluate the qualitative and quantitative toxicity of intratumoral Ad-p53 in this patient population. OUTLINE: This is a dose-escalation, multicenter study. Patients receive an initial intratumoral stereotactic injection of adenovirus p53 (Ad-p53) over 10 minutes on day 1. In the absence of unacceptable toxicity resulting from this initial injection, patients then undergo tumor resection and receive a series of 1-minute injections of Ad-p53 into the resected tumor cavity wall on day 4. Cohorts of 3-6 patients receive escalating doses of Ad-p53. If 2 of 3 or 3 of 6 patients experience dose limiting toxicity (DLT) at a particular dose level, escalation ceases and the maximum tolerated dose is defined as the previous dose level. Patients are followed closely for 12 weeks, then every 2 weeks for 8 weeks, then every 4 weeks for 8 weeks, and then every 8 weeks until death. PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study.

Official Title
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Phase I Trial of Adenovirus-Mediated Wild-Type P53 Gene Therapy for Malignant Gliomas

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Biological: Ad5CMV-p53 gene
* Procedure: conventional surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven malignant primary glioma Glioblastoma multiforme Anaplastic oligodendroglioma Gliosarcoma Mixed malignant glioma Anaplastic astrocytoma Clear evidence of tumor recurrence or progression by CT or MRI within 2 weeks prior to study after failing prior best surgical resection and radiation Surgically accessible tumor for which resection is indicated Tumors greater than 2.0 cm in diameter Tumor not extending into the ventricular system PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100% Life expectancy: Not specified Hematopoietic: Absolute granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 No evidence of bleeding diatheses Hepatic: SGPT no greater than 2 times upper limit of normal (ULN) Alkaline phosphatase no greater than 2 times ULN Bilirubin less than 1.5 mg/dL Renal: BUN less than 1.5 times ULN OR Creatinine less than 1.5 times ULN Cardiovascular: Not specified Pulmonary: Not specified Other: No active uncontrolled infection Must be afebrile (less than 38.0 degrees Celsius) No other unstable or serious medical conditions HIV negative Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Prior chemotherapy allowed (at least 2 weeks since prior vincristine, 3 weeks since prior procarbazine, and 6 weeks since prior nitrosoureas) and recovered Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics At least 4 weeks since prior radiotherapy Surgery: See Disease Characteristics Other: No prior or concurrent anticoagulants

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: Ad5CMV-p53 gene|nan|
|Procedure: conventional surgery|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult brain tumor, adult glioblastoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma, adult giant cell glioblastoma, adult gliosarcoma