RATIONALE: The measles virus, that has been changed in a certain way, may kill tumor cells without damaging normal cells.

PURPOSE: This phase I trial is studying the side effects and best dose of viral therapy in treating patients with recurrent glioblastoma multiforme.

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 stereotactic biopsy (to confirm the diagnosis) and 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.

DISEASE CHARACTERISTICS:

• Histologically confirmed grade 4 astrocytoma (glioblastoma multiforme) at primary diagnosis and/or recurrence
• Recurrent disease

• Candidate for gross total or subtotal resection

  • No expected communication between ventricles and resection cavity as a result of surgery
• Antimeasles virus immunity as demonstrated by IgG antimeasles antibody levels of ≥ 20 EU/mL as determined by enzyme immunoassay
• Human carcinoembryonic antigen (CEA) < 3 ng/mL

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST ≤ 2 times ULN
• Creatinine ≤ 2.0 times ULN
• Hemoglobin ≥ 9.0 g/dL
• PT and aPTT ≤ 1.3 times ULN
• Willing to provide biological specimens as required by the study
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection within the past 5 days
• No history of tuberculosis or purified protein derivative positivity
• No New York Heart Association class III or IV cardiac disease
• Adequate seizure control
• HIV negative
• No history of other immunodeficiency
• No history of chronic hepatitis B or C
• No exposure (household contacts) to children ≤ 15 months of age or to people with known immunodeficiency
• No allergy to measles vaccine or history of severe reaction to prior measles vaccination
• No requirement for blood product support

PRIOR CONCURRENT THERAPY:

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosourea-based chemotherapy) and recovered
• More than 4 weeks since prior immunotherapy
• More than 4 weeks since prior biologic therapy
• More than 2 weeks since prior noncytotoxic antitumor drugs (i.e., small molecule cell cycle inhibitors)
• More than 6 weeks since prior radiotherapy
• No prior viral or gene therapy
• No history of organ transplantation
• No concurrent chemotherapy, other immunotherapy, radiotherapy, or any other ancillary therapy considered investigational (utilized for a non-FDA-approved indication and in the context of a research investigation)
• No concurrent enrollment on any other study involving a pharmacologic agent (e.g., drugs, biologics), immunotherapy approaches, or gene therapy whether for symptom control or therapeutic intent