Gene Therapy in Treating Patients With Recurrent Malignant Gliomas

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004041
• Other study ID #: NABTC-9703
• Secondary ID: CDR0000066871
• Status: Completed
• Phase: Phase 1
• Start date: February 25, 1999
• Est. completion date: July 1, 2003

Study information

• Verified date: June 2018
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: July 1, 2003
• Est. primary completion date: July 22, 2002
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioma
• Nervous System Neoplasms

Intervention

Biological:
• Ad5CMV-p53 gene

Procedure:
• conventional surgery

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,