Gene Therapy in Treating Patients With Recurrent Malignant Gliomas

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Completed

CT.gov ID

NCT00004041

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

52.1

Actual Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Biological: Ad5CMV-p53 gene Procedure: conventional surgery	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 25, 1999

Actual Primary Completion Date :

Jul 22, 2002

Actual Study Completion Date :

Jul 1, 2003

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Cancer Center and Cancer Research Institute	San Francisco	California	United States	94115-0128
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
3	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0752
4	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15213
5	Simmons Cancer Center - Dallas	Dallas	Texas	United States	75235-9154
6	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030
7	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811
8	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792