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
  Purpose

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.


Condition Intervention Phase
Adult Brain Tumor
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Biological: carcinoembryonic antigen-expressing measles virus
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of a Measles Virus Derivative Producing CEA (MV-CEA) in Patients With Recurrent Glioblastoma Multiforme (GBM)

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 40
Study Start Date: October 2006
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Biological: carcinoembryonic antigen-expressing measles virus
Given IV
Other Name: MV-CEA
Procedure: therapeutic conventional surgery Other: laboratory biomarker analysis
Correlative study

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00390299

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Evanthia Galanis         
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Evanthia Galanis Mayo Clinic
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00390299     History of Changes
Other Study ID Numbers: MC0671, NCI-2009-01198, MC0671, P30CA015083
Study First Received: October 18, 2006
Last Updated: August 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioblastoma
Brain Neoplasms
Neoplasms
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on October 01, 2014