Phase I Trial of a Measles Virus Derivative Producing CEA (MV-CEA) in Patients With Recurrent Glioblastoma Multiforme (GBM)
Trial status: Open for Enrollment
Why is this study being done?
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?
- 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
- 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