Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme

Mayo Clinic

Status and phase: Completed; Phase 1

Conditions: Recurrent Glioblastoma; Mixed Glioma; Anaplastic Oligodendroglioma; Anaplastic Astrocytoma

Treatments: Other: Laboratory Biomarker Analysis; Procedure: Therapeutic Conventional Surgery; Biological: Carcinoembryonic Antigen-Expressing Measles Virus

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00390299

P30CA015083 (U.S. NIH Grant/Contract)

MC0671 (Other Identifier)

P50CA108961 (U.S. NIH Grant/Contract)

NCI-2009-01198 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 23 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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23 participants in 2 patient groups

Arm A (resection cavity administration)

Experimental group

Description:

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

Treatment:

Biological: Carcinoembryonic Antigen-Expressing Measles Virus

Procedure: Therapeutic Conventional Surgery

Other: Laboratory Biomarker Analysis

Arm B (intratumoral and resection cavity administration)

Experimental group

Description:

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.

Treatment:

Biological: Carcinoembryonic Antigen-Expressing Measles Virus

Procedure: Therapeutic Conventional Surgery

Other: Laboratory Biomarker Analysis