Clinical trial NCT00390299: Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme
Official title: Phase I Trial of a Measles Virus Derivative Producing CEA (MV-CEA) in Patients With Recurrent Glioblastoma Multiforme (GBM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Anaplastic Astrocytoma
Anaplastic Oligodendroglioma
Mixed Glioma
Recurrent Glioblastoma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-10-19
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I) Maximum Tolerated Dose (MTD) (Phase I) as Measured by the Number of Participants With Dose Limiting Toxicities
timeFrame: 2 weeks
measure: Number of Patients Experiencing Grade 3+ Adverse Events, Per NCI CTCAE Version 3.0
timeFrame: Up to 2 weeks
Secondary outcomes:
measure: Best Response, Defined as the Best Objective Status Recorded From the Start of the Treatment Until Disease Progression/Recurrence
timeFrame: Up to 2 weeks
measure: Progression-free Survival (PFS)
timeFrame: Length of time from date of registration to a) date of progression or death due to any cause or b) last follow-up, assessed up to 6 months
measure: Survival
timeFrame: Up to 13 years
Other outcomes:
measure: CEA Titers
timeFrame: Up to 15 years
measure: Change in CD4 Counts
timeFrame: Baseline to day 28
measure: Change in CD46 Status
timeFrame: Baseline to up to day 5
measure: Change in CD8 Counts
timeFrame: Baseline to day 28
measure: Change in Viral Shedding
timeFrame: Baseline to day 28
measure: Change in Viremia
timeFrame: Baseline to up to 15 years
measure: Measles Virus Specific Immunity, in Terms of Change in Interferon Gamma
timeFrame: Baseline to day 28
measure: Measles Virus Specific Immunity, in Terms of Change in Lymphoproliferative Assay Results
timeFrame: Baseline to day 28
measure: Viral Propagation in Tumor
timeFrame: Up to day 5
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Evanthia Galanis
role: PRINCIPAL_INVESTIGATOR
References: