Phase I Trial of a Measles Virus Derivative Producing CEA (MV-CEA) in Patients With Recurrent Glioblastoma Multiforme (GBM)

Location:

Rochester, Minn.

Trial status:

Open for Enrollment

Why is this study being done?

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 asses 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: Patients are assigned to 1 or 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. After completion of study treatment, patients are followed periodically for up to 15 years.

Who is eligible to participate?

Inclusion Criteria: - PLT >= 100,000/uL - Must have central review prior to registration - Candidate for gross total or subtotal resection - Ability to provide informed consent - Willing to provide biological specimens as required by the protocol - Normal serum CEA level (< ng/ml) at the time of registration - Recurrent grade 4 astrocytoma and grade 4 gliosarcoma with histological confirmation at primary diagnosis and/or recurrence - Negative serum pregnancy test done =< 7 days prior to registration (for women of childbearing potential only) - Anti-measles virus immunity as demonstrated by IgG anti-measles antibody levels of >= 20 EU/ml as determined by Enzyme Immunoassay - Grade 3 astrocytoma patients with clinical or imaging characteristics suggestive of progression to grade 4 are eligible, provided that the diagnosis of grade 4 astrocytoma is confirmed by biopsy (including confirmation in frozen section) prior to viral administration - Total bilirubin =< 1.5 x upper normal limit (ULN) - AST =< 2 x ULN - Creatinine =< 2.0 x ULN - Hgb >= 9.0 gm/dL - PT and aPTT =< 1.3 x ULN - ECOG performance status (PS) 0, 1 or 2 - ANC >= 1500/uL Exclusion Criteria: - Pregnant women - Nursing women - 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 IV - Requiring blood product support - Inadequate seizure control - Expected communication between ventricles and resection cavity as a result of surgery - History of organ transplant - History of chronic hepatitis B or C - Exposure to household contact =< 15 months old or household contact with known immunodeficiency - Allergy to measles vaccine or history of severe reaction to prior measles vaccination - Chemotherapy =< 4 weeks prior to registration (6 wks for nitrosourea-based chemotherapy) - Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-FDA -approved indication and in the context of research investigation) - History of tuberculosis or history of PPD positivity - Biologic therapy =< 4 weeks prior to registration - Non-cytotoxic antitumor drugs (i.e., small molecular cell cycle inhibitors) =< 2 weeks prior to registration - HIV-positive test result or history of other immunodeficiency - Men or women of childbearing potential who are unwilling to employ adequate contraception - Active infection =< 5 days prior to registration - Immunotherapy =< 4 weeks prior to registration

Last updated:

10/27/2014

NCT ID:

NCT00390299

IRB Number:

06-004440