A Phase 1 Trial of Oncolytic Measles Virotherapy in Mesothelioma
Maximum tolerated dose (MTD) for the intrapleural administration of a modified vaccine
strain measles virus (MV) genetically engineered to produce human thyroidal sodium iodine
symporter (NIS) (MV-NIS [oncolytic measles virus encoding thyroidal sodium iodide
symporter])in patients with MPM.
Safety and toxicity of the repeated (up to 6 cycles) intrapleural administration of MV-NIS
in patients with malignant pleural mesothelioma.
I. Time course of viral infection, dissemination and elimination by non-invasive
measurements of NIS gene expression using radioactive iodine and single-photon emission
computed tomography (SPECT)/ computed tomography (CT) imaging with.
II. Viremia, viral replication, and viral shedding following intrapleural administration.
III. Changes in humoral and cellular anti-MV immunity following the intrapleural
administration of MV-NIS.
IV. Antitumor efficacy of this approach by serial measurements of radioiodine uptake by
SPECT/CT, radiographic response, and time to disease progression.
V. Changes in both local and systemic innate and adaptive anti-tumor immunity following the
intrapleural administration of MV-NIS.
VI. Effect of MV-NIS administration on the eukaryotic initiation factor (eIF) 4F translation
complex in mesothelioma cells.
OUTLINE: This is a dose-escalation study.
Patients receive the oncolytic measles virus encoding thyroidal sodium iodide symporter
(MV-NIS) intrapleurally. In the absence of unacceptable side effects or disease progression
treatment can be repeated every 28 days for up to 6 courses.
After completion of study treatment, patients are followed up every 3 to 6 months for up to
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Adverse event (AE) profile
The number and severity of toxicity incidents will indicate the level of tolerance for MV-NIS in the therapy of MPM. Non-hematologic toxicities will be evaluated via the CTCAE v4.0 standard toxicity grading. Hematologic toxicity measures such as anemia, neutropenia and thrombocytopenia will be assessed using continuous variables as the outcome measures (nadir and percent change from baseline values) as well as categorization via CTCAE v4.0 standard toxicity grading. Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
United States: Food and Drug Administration
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