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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
23
Given via injection into resection cavity or around tumor bed and/or IT
Correlative studies
Undergo en bloc resection
Mayo Clinic
Rochester, Minnesota, United States
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
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.
Time frame: 2 weeks
Number of Patients Experiencing Grade 3+ Adverse Events, Per NCI CTCAE Version 3.0
The number of patients experiencing grade 3+ adverse events (overall and by arm) will be tabulated and summarized in this patient population.
Time frame: Up to 2 weeks
Best Response, Defined as the Best Objective Status Recorded From the Start of the Treatment Until Disease Progression/Recurrence
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.
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Time frame: Up to 2 weeks
Progression-free Survival (PFS)
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.
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
Survival
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.
Time frame: Up to 13 years