Clinical Trial Finder

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

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.

Arms

Experimental: 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.

Experimental: 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 MV-CEA 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.

Interventions

Biological: - Carcinoembryonic Antigen-Expressing Measles Virus

Given via injection into resection cavity or around tumor bed and/or IT

Other: - Laboratory Biomarker Analysis

Correlative studies

Procedure: - Therapeutic Conventional Surgery

Undergo en bloc resection