Clinical Trials

Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme

Location:

Rochester, MN

Trial status:

Open for Enrollment

Why is this study being done?

OBJECTIVES: Primary - Determine the safety and toxicity of intratumoral and/or resection cavity administration of a recombinant, attenuated Edmonston B vaccine strain derivative of measles virus genetically engineered to produce human carcinoembryonic antigen (CEA) in patients with recurrent glioblastoma multiforme. - Determine the maximum tolerated dose of this oncolytic virus in these patients. - Determine viral gene expression at each dose level as manifested by CEA titers in patients treated with this oncolytic virus. - Assess viremia, viral replication, and measles virus shedding/persistence after intratumoral administration of this oncolytic virus. - Assess humoral and cellular immune response to the injected virus in these patients. Secondary - Determine, preliminarily, the antitumor efficacy of this vaccine in these patients. OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 sequential treatment groups. - Group 1 (resection cavity administration): Patients undergo en block resection of their tumor (after confirming diagnosis) on day 1, followed by recombinant measles virus encoding human carcinoembryonic antigen (MV-CEA) administered into the resection cavity over 10 minutes. - Group 2 (intratumoral and resection cavity administration): Patients undergo placement of a catheter within the tumor, followed by MV-CEA administration into the tumor through the catheter over 10 minutes on day 1. Patients undergo en block resection of their tumor with computer-assisted stereotactic techniques on day 5, followed by MV-CEA administered around the tumor bed. In both groups, cohorts of 1-6 patients receive escalating doses of MV-CEA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD in group 1 has been determined, patients are assigned to group 2. The MTD in group 1 is used to determine the starting dose in group 2. At least 10 patients are treated at the MTD determined in group 2. Biopsy specimen, resected tumor, normal tissue, and peripheral blood are collected during study for immunologic and biomarker correlative studies, including analysis of CD46 receptor levels (by immunohistochemistry [IHC]), measles virus N protein (by IHC), measles and viral gene expression and replication (by in situ hybridization), CEA monitoring (by immunoassay), measles virus N mRNA (by reverse transcriptase-polymerase chain reaction), and measles virus immunity. Assessments of immune competence and peripheral response to viral administration are also performed. After completion of study treatment, patients are followed periodically for up to 15 years. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Last updated: 11/28/2012

NCT ID:

NCT00390299