Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme
Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme
This phase I trial studies the side effects and best dose of carcinoembryonic
 antigen-expressing measles virus (MV-CEA) in treating patients with glioblastoma multiforme
 that has come back. A virus, called MV-CEA, which has been changed in a certain way, may be
 able to kill tumor cells without damaging normal cells.
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