Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00390299
First received: October 18, 2006
Last updated: August 7, 2014
Last verified: August 2014

October 18, 2006
August 7, 2014
October 2006
June 2015   (final data collection date for primary outcome measure)
  • Toxicity profile as assessed by NCI CTC version 3.0 [ Designated as safety issue: Yes ]
  • Adverse events profile [ Designated as safety issue: Yes ]
  • Response profile [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00390299 on ClinicalTrials.gov Archive Site
  • Time until any treatment related toxicity, time until treatment related grade 3+ toxicity, and time until hematologic nadir (WBC, ANC, platelets) [ Designated as safety issue: Yes ]
  • Time to progression and time time to treatment failure [ Designated as safety issue: No ]
  • Laboratory correlates [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme
Phase I Trial of a Measles Virus Derivative Producing CEA (MV-CEA) in Patients With Recurrent Glioblastoma Multiforme (GBM)

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.

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.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Adult Brain Tumor
  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Recurrent Adult Brain Tumor
  • Biological: carcinoembryonic antigen-expressing measles virus
    Given IV
    Other Name: MV-CEA
  • Procedure: therapeutic conventional surgery
  • Other: laboratory biomarker analysis
    Correlative study
Experimental: Arm I

Patients are assigned to 1 of 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.

Interventions:
  • Biological: carcinoembryonic antigen-expressing measles virus
  • Procedure: therapeutic conventional surgery
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
40
Not Provided
June 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
United States
 
NCT00390299
MC0671, NCI-2009-01198, MC0671, P30CA015083
No
Mayo Clinic
Mayo Clinic
National Cancer Institute (NCI)
Principal Investigator: Evanthia Galanis Mayo Clinic
Mayo Clinic
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP