This phase I trial studies the side effects and the best dose of a vaccine therapy in treating patients with malignant peripheral nerve sheath tumor that cannot be removed by surgery (unresectable) or has come back after a period of improvement (recurrent). Vaccines made from a gene-modified virus may kill tumor cells expressing a gene called neurofibromin 1 (NF1) without affecting surrounding normal cells and may also help the body build an effective immune response to kill tumor cells.
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of intratumoral administration of an Edmonston strain measles virus genetically engineered to express neurofibromatosis type 1 (NIS) (oncolytic measles virus encoding thyroidal sodium iodide symporter \[MV-NIS\]) in patients with inoperable or recurrent malignant peripheral nerve sheath tumor (MPNST). II. To determine the safety and toxicity of intratumoral administration of MV-NIS in patients with inoperable recurrent MPNST. III. To preliminarily assess antitumor efficacy of intratumoral MV-NIS administration by the rate of progression-free survival at 3 months, achieved by following radiographic response of the treated lesion using World Health Organization (WHO) response criteria guidelines. SECONDARY OBJECTIVES: I. To determine the time course of viral gene expression and virus elimination and biodistribution of virally infected cells at various time points after infection with MV-NIS using single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging. II. To assess viremia, viral replication, and measles virus shedding/persistence following intratumoral administration. III. To determine humoral and cellular immune response to the injected virus. IV. To assess the quality-of-life of patients treated with MV-NIS, using two inventories (Pain and Fatigue). V. To assess time to progression and differences in growth rates between treated and untreated tumor lesions. VI. To assess the overall survival time of patients treated with MV-NIS. OUTLINE: Patients receive MV-NIS intratumorally on day 1. Patients also undergo SPECT/CT at baseline and at 3 and 8 days after MV-NIS. Patients may also undergo SPECT/CT at 15 and 28 days, and at 6 weeks based on whether there is uptake on prior imaging studies. Patients also undergo magnetic resonance imaging (MRI), ultrasound imaging, blood sample collection and tissue biopsy throughout the trial. After completion of study treatment, patients are followed up at 3, 6, 12, 18, and 24 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Undergo CT scan
Correlative studies
Given intratumorally
Ancillary studies
Undergo SPECT imaging
Undergo MRI
Undergo ultrasound imaging
Undergo blood sample collection
Undergo tissue biopsy
Ancillary studies
Mayo Clinic
Rochester, Minnesota, United States
Best response using the World Health Organization response criteria
Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and dose level).
Time frame: From the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started), assessed up to 2 years
Incidence of adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
The number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion. Overall toxicity incidence as well as 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.
Time frame: Up to 2 years after treatment
Maximum tolerated dose defined as the highest safely tolerated dose level where at most 1 out of 6 patients experience dose-limiting toxicity (DLT) with the next higher dose having at least 2 patients out of a maximum of 6 patients experience DLT
Assessed according to according to Common Terminology Criteria for Adverse Events version 4.0. The number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized in this patient population.
Time frame: 6 weeks
Absolute percentage change in quality of life measured using the Brief Pain Inventory (short form) and Brief Fatigue Inventory
Determination of significant changes in quality of life over time will be assessed using a signed rank test comparing the change at each assessment point from baseline. Quality of life will be used as a descriptive supplement to other clinical information. Simple exploratory analysis may be undertaken to look for changes in quality of life scores over time as well as associations between change in quality of life scores at different time points and per dose level.
Time frame: Baseline to up to 2 years
Change in biodistribution of virally infected cells at various time points after infection with MV-NIS using single photon emission computed tomography/computed tomography
Patients may be imaged on days 15, 28 and week 6. Absolute and percent change from baseline along with t-tests to evaluate change from baseline to all observed timepoints.
Time frame: Baseline to up to day 8
Growth-rate between treated and untreated lesions
Differences in growth-rate between treated and untreated lesions will be compared using paired t-tests.
Time frame: Up to 2 years
Humoral and cellular immune response to the injected virus
Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
Time frame: Up to 2 years
Incidence of measles virus shedding/persistence following intratumoral administration
Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures like response, and dose levels will be carried out in an exploratory manner.
Time frame: Up to 2 years
Incidence of viral replication following intratumoral administration
Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures like response, and dose levels will be carried out in an exploratory manner.
Time frame: Up to 2 years
Incidence of viremia following intratumoral administration
Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures like response, and dose levels will be carried out in an exploratory manner.
Time frame: Up to 2 years
Progression-free survival by radiographic response of the treated lesion using World Health Organization response criteria guidelines
A progression-free survival at 3 months success is defined as a patient who is alive and their treated lesion is progression free at three months after they have treatment with oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS).
Time frame: At 3 months
Time to progression
Time frame: Up to 2 years
Time until hematologic nadirs (absolute neutrophil count, platelets, hemoglobin)
Time frame: Up to 2 years
Viral gene expression
Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures like response, and dose levels will be carried out in an exploratory manner.
Time frame: Up to 2 years
Virus elimination as monitored by single photon emission computed tomography/computed tomography imaging
Patients may be imaged on days 15, 28 and week 6. Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Absolute and percent change from baseline along with t-Tests to evaluate change from baseline to all observed timepoints.
Time frame: Up to day 8
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