Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme

PRIMARY OBJECTIVES:

I. To assess the safety and toxicity of intratumoral and resection cavity administration of
an Edmonston's strain measles virus genetically engineered to produce CEA (MV-CEA) in
patients with recurrent glioblastoma multiforme.

II. To determine the maximum tolerated dose (MTD) of MV-CEA. III. To characterize viral gene
expression at each dose level as manifested by CEA titers.

IV. To assess viremia, viral replication, and measles virus shedding/persistence following
intratumoral administration.

V. To assess humoral and cellular immune response to the injected virus. VI. To assess in a
preliminary fashion antitumor efficacy of this approach.

OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 sequential
treatment arms.

ARM A (RESECTION CAVITY ADMINISTRATION): Patients undergo en block resection of their tumor
(after confirming diagnosis) on day 1, followed by MV-CEA administered into the resection
cavity.

ARM B (INTRATUMORAL AND RESECTION CAVITY ADMINISTRATION): Patients undergo stereotactic
biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by
carcinoembryonic antigen-expressing measles virus intratumorally (IT) through the catheter
over 10 minutes on day 1. Patients then undergo en block resection of their tumor with
computer-assisted stereotactic techniques on day 5, followed by MV-CEA administered around
the tumor bed.

After completion of study treatment, patients are followed up at 28 days (non-cohort I
patients), 7 weeks (patients in cohort I only), every 2 months until progression, every 3 and
12 months after progression, and then yearly thereafter for up to 15 years.

Inclusion Criteria:

- Recurrent grade 3 or 4 glioma, including astrocytoma, oligodendroglioma or mixed
glioma with histologic confirmation at initial diagnosis or recurrence

- Candidate for gross total or subtotal resection

- Absolute neutrophil count (ANC) >= 1500/uL

- Platelets (PLT) >= 100,000/uL

- Total bilirubin =< 1.5 x upper normal limit (ULN)

- Aspartate aminotransferase (AST) =< 2 x ULN

- Creatinine =< 2.0 x ULN

- Hemoglobin (Hgb) >= 9.0 gm/dL

- Prothrombin time (PT) and activated partial thromboplastin time (aPTT) =< 1.3 x ULN

- Ability to provide informed consent

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

- Anti-measles virus immunity as demonstrated by immunoglobulin G (IgG) anti-measles
antibody levels of >= 1.1 EU/ml as determined by enzyme immunoassay

- Normal serum CEA levels (< 3 ng/ml) at the time of registration

- Willing to provide biologic specimens as required by the protocol

- Negative serum pregnancy test done =< 7 days prior to registration (for women of
childbearing potential only)

Exclusion Criteria:

- Any of the following:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception

- Active infection =< 5 days prior to registration

- History of tuberculosis or history of purified protein derivative (PPD) positivity

- Any of the following therapies:

- Chemotherapy =< 4 weeks prior to registration (6 wks for nitrosourea-based
chemotherapy)

- Immunotherapy =< 4 weeks prior to registration

- Biologic therapy =< 4 weeks prior to registration

- Bevacizumab =< 12 weeks prior to registration

- Non-cytotoxic antitumor drugs, i.e., small molecule cell cycle inhibitors =< 2
weeks prior to registration

- Radiation therapy =< 6 weeks prior to registration

- Any viral or gene therapy prior to registration

- Failure to fully recover from acute, reversible effects of prior chemotherapy
regardless of interval since last treatment

- New York Heart Association classification III or IV

- Requiring blood product support

- Inadequate seizure control

- Expected communication between ventricles and resection cavity as a result of surgery

- Human immunodeficiency virus (HIV)-positive test result, or history of other
immunodeficiency

- History of organ transplantation

- History of chronic hepatitis B or C

- Other concurrent chemotherapy, immunotherapy, radiotherapy or any ancillary therapy
considered investigational (utilized for a non-Food and Drug Administration
[FDA]-approved indication and in the context of a research investigation)

- Exposure to household contacts =< 15 months old or household contact with known
immunodeficiency

- Allergy to measles vaccine or history of severe reaction to prior measles vaccination