Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by Mayo Clinic
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00390299
First received: October 18, 2006
Last updated: April 19, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention Phase
Adult Anaplastic Astrocytoma
Adult Anaplastic Oligodendroglioma
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Adult Mixed Glioma
Recurrent Adult Brain Neoplasm
Biological: Carcinoembryonic Antigen-Expressing Measles Virus
Other: Laboratory Biomarker Analysis
Procedure: Therapeutic Conventional Surgery
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
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:
  • MTD, defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least 1/3 of patients (at least 2/6 new patients) or the highest dose level for Arm B, if =< 1/6 patients experience dose-limiting toxicity [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
  • Number and severity of all adverse events, per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Up to 15 years ] [ Designated as safety issue: Yes ]
    The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population.

  • Number and severity of grade 3+ adverse events, per NCI CTCAE version 3.0 [ Time Frame: Up to 15 years ] [ Designated as safety issue: Yes ]
    The number and severity of grade 3+ adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population.

  • Overall toxicity incidence, per NCI CTCAE version 3.0 [ Time Frame: Up to 15 years ] [ Designated as safety issue: Yes ]
    Overall toxicity incidence will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  • Time until any treatment related toxicity [ Time Frame: Up to 15 years ] [ Designated as safety issue: Yes ]
  • Time until hematologic nadir (white blood cells [WBC], ANC, platelets) [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
  • Time until treatment related grade 3+ toxicity [ Time Frame: Up to 15 years ] [ Designated as safety issue: Yes ]
  • Toxicity profile by dose level, patient, and tumor site, per NCI CTCAE version 3.0 [ Time Frame: Up to 15 years ] [ Designated as safety issue: Yes ]
    Toxicity profiles by dose level, patient, and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.


Secondary Outcome Measures:
  • Best response, defined as the best objective status recorded from the start of the treatment until disease progression/recurrence [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
    The number of responses will be summarized by simple descriptive summary statistics delineating response type (complete response vs partial response vs regression), as well as stable and progressive disease in this patient population.

  • Progression-free survival (PFS) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Percentage of patients who are progression free at 3 and 6 months (PFS3 and PFS6) will be summarized descriptively.

  • Survival [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
    Reported using standard Kaplan-Meier estimation method.

  • Time to disease progression [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
    Reported using standard Kaplan-Meier estimation method.

  • Time to treatment failure [ Time Frame: Time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 15 years ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • CEA titers [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlates between these laboratory values and other outcome measures like response and dose levels will be carried out in an exploratory manner.

  • Change in CD4 counts [ Time Frame: Baseline to day 28 ] [ Designated as safety issue: No ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlates between these laboratory values and other outcome measures like response and dose levels will be carried out in an exploratory manner.

  • Change in CD46 status [ Time Frame: Baseline to up to day 5 ] [ Designated as safety issue: No ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlates between these laboratory values and other outcome measures like response and dose levels will be carried out in an exploratory manner.

  • Change in CD8 counts [ Time Frame: Baseline to day 28 ] [ Designated as safety issue: No ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlates between these laboratory values and other outcome measures like response and dose levels will be carried out in an exploratory manner.

  • Change in viral shedding [ Time Frame: Baseline to day 28 ] [ Designated as safety issue: No ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlates between these laboratory values and other outcome measures like response and dose levels will be carried out in an exploratory manner.

  • Change in viremia [ Time Frame: Baseline to up to 15 years ] [ Designated as safety issue: No ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlates between these laboratory values and other outcome measures like response and dose levels will be carried out in an exploratory manner.

  • Measles virus specific immunity, in terms of change in interferon gamma [ Time Frame: Baseline to day 28 ] [ Designated as safety issue: No ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlates between these laboratory values and other outcome measures like response and dose levels will be carried out in an exploratory manner.

  • Measles virus specific immunity, in terms of change in lymphoproliferative assay results [ Time Frame: Baseline to day 28 ] [ Designated as safety issue: No ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlates between these laboratory values and other outcome measures like response and dose levels will be carried out in an exploratory manner.

  • Viral propagation in tumor [ Time Frame: Up to day 5 ] [ Designated as safety issue: No ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlates between these laboratory values and other outcome measures like response and dose levels will be carried out in an exploratory manner.


Estimated Enrollment: 40
Study Start Date: October 2006
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: Carcinoembryonic Antigen-Expressing Measles Virus
Given via injection into resection cavity or around tumor bed and/or intratumorally
Other Name: MV-CEA
Other: Laboratory Biomarker Analysis
Correlative studies
Procedure: Therapeutic Conventional Surgery
Undergo en bloc resection
Experimental: 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 administered into the tumor 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.
Biological: Carcinoembryonic Antigen-Expressing Measles Virus
Given via injection into resection cavity or around tumor bed and/or intratumorally
Other Name: MV-CEA
Other: Laboratory Biomarker Analysis
Correlative studies
Procedure: Therapeutic Conventional Surgery
Undergo en bloc resection

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 administered into the tumor 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, 3 months after progression, 12 months after progression, and then yearly thereafter for up to 15 years.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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
National Cancer Institute (NCI)
Investigators
Principal Investigator: Evanthia Galanis Mayo Clinic
  More Information

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: April 19, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Gliosarcoma
Oligodendroglioma
Brain Neoplasms
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
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 July 24, 2016