Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme

NCT ID: NCT00390299

Last Updated: 2020-01-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-23
• Study Completion Date: 2019-11-30

Brief Summary

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.

Detailed 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.

Conditions

Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Mixed Glioma; Recurrent Glioblastoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Carcinoembryonic Antigen-Expressing Measles Virus

Intervention Type: BIOLOGICAL

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

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Therapeutic Conventional Surgery

Intervention Type: PROCEDURE

Undergo en bloc resection

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.

Group Type: EXPERIMENTAL

Carcinoembryonic Antigen-Expressing Measles Virus

Intervention Type: BIOLOGICAL

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

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Therapeutic Conventional Surgery

Intervention Type: PROCEDURE

Undergo en bloc resection

Interventions

Carcinoembryonic Antigen-Expressing Measles Virus

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

Intervention Type: BIOLOGICAL

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Therapeutic Conventional Surgery

Undergo en bloc resection

Intervention Type: PROCEDURE

Other Intervention Names

MV-CEA

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Evanthia Galanis

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2009-01198

Identifier Type: REGISTRY

Identifier Source: secondary_id

MC0671

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P50CA108961

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MC0671

Identifier Type: -

Identifier Source: org_study_id