Phase I Trial of a Measles Virus Derivative Producing CEA (MV-CEA) in Patients With Recurrent Glioblastoma Multiforme (GBM)
- 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.
- 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
- 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.
Primary Purpose: Treatment
Adverse events profile, in terms of number and severity of all adverse events, as assessed by NCI CTCAE v3.0
Evanthia Galanis, MD
United States: Food and Drug Administration
|Mayo Clinic Cancer Center||Rochester, Minnesota 55905|