Phase II Trial of Poly-ICLC in Pediatric Low Grade Gliomas

Background
Brain tumors are the most common solid tumor diagnosed in childhood and thus account for significant childhood mortality in the United States. Low-grade astrocytomas and gliomas (LGG) are the most common type of brain tumor of childhood (36% of childhood brain tumors). Radiotherapy is avoided or delayed in the treatment of LGG to prevent neurocognitive decline and to prevent transformation to more malignant grade of tumor (grade III and IV). 

A previous clinical trial of a double stranded RNA molecule, polyinosinic-polycytidylic acid termed polyICLC (a TLR3 agonist) was carried out by the PI in 43 patients diagnosed with pediatric brain tumors (all brain tumor subtypes). The results from this Phase II trial suggest that the low grade glioma cohort had the best response to this therapy (50% response rate). To test this hypothesis, in the current Phase II trial we designed a trial only in low grade glioma patients.

Project Goal and Potential Impact

In this proposal, we hypothesize that LGG are more likely to respond to this TLR3 agonist and that characterization of signaling pathways for TLR3 in tumor and stromal compartment will allow us to identify the patients most likely to respond to this therapy.  The significance of our proposal derives from the unmet medical need for alternative therapy for patients with recurrent LGG. If successful, this therapy could provide a significant advancement in the quality of treatment for this difficult to treat disease.