A Non-randomized, Open-label Dose-finding Trial of Combined Cytotoxic and Immune-Stimulatory Strategy for the Treatment of Resectable Primary Malignant Glioma
This is a Phase 1, multiple center open label, dose escalation safety study of Ad-hCMV-TK
and Ad-hCMV-Flt3L delivered to the peritumoral region after tumor resection. This study will
combine direct tumor cell killing (TK) and immune-mediated stimulatory (Flt3L) gene transfer
approaches delivered by first generation adenoviral vectors. Treatment with HSV1-TK is
expected to kill transduced brain cells, thus exposing tumor antigen. Treatment with Flt3L,
a cytokine known to cause proliferation of dendritic cells, should cause the migration of
dendritic cells to the peritumoral brain and remaining tumor. There, they will be exposed to
tumor antigens released from dying glioma cells through TK + valacyclovir-induced glioma
cell death, and thus mediate a specific anti-malignant glioma immune response against
remaining malignant glioma cells.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose-Limiting Toxicity
Grade 4 toxicity for constitutional symptoms as graded by the NCI Common Terminology Criteria for Adverse Events v4.03 (CTCAE) with the exception of fever >40°C for ≤24 hours. Grade 3 or greater CTCAE v4.03 neurologic toxicity relative to the changes from the pre-treatment neurological status and attributable to the study therapy regimen. Grade 3 or greater non hematologic toxicity as defined by CTCAE v.4.03, and attributable to the study therapy regimen. Grade 2 or greater autoimmune events as defined by CTCAE v.4.03
24 months
Yes
Pedro Lowenstein, MD, PhD
Principal Investigator
University of Michigan
United States: Food and Drug Administration
HUM00057130
NCT01811992
March 2013
March 2018
Name | Location |
---|---|
University of Michigan Health System Department of Neurosurgery | Ann Arbor, Michigan 48109 |