Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme
Conditions
Adult Brain Tumor - Adult Giant Cell Glioblastoma - Adult Glioblastoma - Adult Gliosarcoma - Recurrent Adult Brain Tumor
Conditions: official terms
Brain Neoplasms - Glioblastoma - Gliosarcoma
Study Type
Interventional
Study Phase
Phase 1
Study Design
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: carcinoembryonic antigen-expressing measles virus Type: Biological
Name: therapeutic conventional surgery Type: Procedure
Name: laboratory biomarker analysis Type: Other
Overall Status
Recruiting
Summary
RATIONALE: Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of viral therapy in treating patients with recurrent glioblastoma multiforme.
Detailed Description
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: 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
Location
Mayo Clinic
Rochester, Minnesota, United States
Status: Recruiting
Contact: Clinical Trials Referral Office - 855-776-0015
Start Date
October 2006
Sponsors
Mayo Clinic
Source
Mayo Clinic
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page