Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT00390299 |
|
Recruitment Status :
Completed
First Posted : October 19, 2006
Results First Posted : January 2, 2020
Last Update Posted : January 2, 2020
|
Sponsor:
Mayo Clinic
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Anaplastic Astrocytoma Anaplastic Oligodendroglioma Mixed Glioma Recurrent Glioblastoma | Biological: Carcinoembryonic Antigen-Expressing Measles Virus Other: Laboratory Biomarker Analysis Procedure: Therapeutic Conventional Surgery | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 23 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (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) |
| Actual Study Start Date : | October 23, 2006 |
| Actual Primary Completion Date : | November 29, 2018 |
| Actual Study Completion Date : | November 30, 2019 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Measles
| Arm | Intervention/treatment |
|---|---|
|
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 IT
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 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.
|
Biological: Carcinoembryonic Antigen-Expressing Measles Virus
Given via injection into resection cavity or around tumor bed and/or IT
Other Name: MV-CEA Other: Laboratory Biomarker Analysis Correlative studies Procedure: Therapeutic Conventional Surgery Undergo en bloc resection |
Primary Outcome Measures :
- 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 [ Time Frame: 2 weeks ]The Maximum Tolerated Dose (MTD) is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose-limiting toxicities include hematologic events grade 3 or higher (except grade 3 ANC lasting < 72 hours), non-hematologic events graded 3 or higher (except grade 3 nausea, vomiting, or diarrhea were to be considered DLT only if patient was receiving the max supportive care and alopecia was not considered dose limiting), neurologic toxicity grade 2 or higher, grade 2 allergic reactions asymptomatic bronchospasm and/or urticarial, grade 3 or higher allergic reactions, viremia lasting for 6 weeks or more from last viral administration deemed at least possibly related to treatment. The number of patients reporting a dose-limiting event are reported.
- Number of Patients Experiencing Grade 3+ Adverse Events, Per NCI CTCAE Version 3.0 [ Time Frame: Up to 2 weeks ]The number of patients experiencing grade 3+ adverse events (overall and by arm) will be tabulated and summarized in this patient population.
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 2 weeks ]The number of responses will be summarized by simple descriptive summary statistics delineating response type. CR = total disappearance of all tumor with patient off corticosteroids or only on adrenal replacement maintenance. PR= 50% reduction in product of perpendicular diameters of contrast enhancement or mass with no new lesions with the patient being on stable or decreased steroid dose. REGR = unequivocal reduction in size of contrast-enhancement or decrease in mass effect as agreed upon independently by primary physician and quality control physicians; no new lesions. SD = failure to qualify for CR, PR, REGR, or PROG. PROG = >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions and/or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions.
- 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 ]Percentage of patients who are progression free at 3 and 6 months (PFS3 and PFS6) will be summarized descriptively. Progression-free survival is defined as the length of time from date of registration to a) date of progression or death due to any cause or b) last follow-up. Progression is defined as a >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions, and/or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions.
- Survival [ Time Frame: Up to 13 years ]Overall survival is defined as the length of time from date of registration to a) death due to any cause or b) last follow-up. Reported using standard Kaplan-Meier estimation method.
Other Outcome Measures:
- CEA Titers [ Time Frame: Up to 15 years ]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 ]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 ]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 ]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 ]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 ]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 ]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 ]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 ]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.
Information from the National Library of Medicine
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, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00390299
Locations
| United States, Minnesota | |
| Mayo Clinic | |
| Rochester, Minnesota, United States, 55905 | |
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Evanthia Galanis | Mayo Clinic |
Study Documents (Full-Text)
Documents provided by Mayo Clinic:
Documents provided by Mayo Clinic:
Study Protocol and Statistical Analysis Plan [PDF] December 9, 2016
| Responsible Party: | Mayo Clinic |
| ClinicalTrials.gov Identifier: | NCT00390299 |
| Other Study ID Numbers: |
MC0671 NCI-2009-01198 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) MC0671 ( Other Identifier: Mayo Clinic ) P30CA015083 ( U.S. NIH Grant/Contract ) P50CA108961 ( U.S. NIH Grant/Contract ) |
| First Posted: | October 19, 2006 Key Record Dates |
| Results First Posted: | January 2, 2020 |
| Last Update Posted: | January 2, 2020 |
| Last Verified: | January 2019 |
Additional relevant MeSH terms:
|
Glioblastoma Astrocytoma Oligodendroglioma Glioma Recurrence Disease Attributes Pathologic Processes |
Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue |