Low-grade astrocytomas and gliomas are the most common type of childhood brain tumor. Although children with low-grade gliomas often survive many years after conventional treatment with surgery and radiotherapy, there can be tremendous morbidity depending on the location of tumor and the effects of therapy. Newer forms of treatment with reduced side effects are much needed. We have designed a phase II trial to examine efficacy and safety of the biological response modifier poly-ICLC in children with low-grade gliomas, and to identify surrogate biomarkers for response to this agent. Poly-ICLC, a synthetic complex of polyinosinic and polycytidylic acid, stabilized with polylysine and carboxymethyl cellulose is a double stranded RNA (dsRNA) that is a ligand for the Toll-like Receptor 3 (TLR3), an important component of innate immunity. It has been shown to have direct antiviral and antineoplastic effects mediated by at least two interferon inducible nuclear enzyme systems of OAS and PKR. A previous Phase I/II trial of poly-ICLC conducted in pediatric patients with brain tumors (all histopathologic subtypes) suggested the low-grade glioma cohort had the best response to this therapy (50% PR rate). Additional clinical trials in adult patients have confirmed that the most responsive subgroup to poly-ICLC is low-grade glioma patients. We are currently conducting a multi-institutional phase II study of poly-ICLC administered at 20mcg/kg/dose intramuscularly twice weekly to children with recurrent or progressive low-grade gliomas. Simon's two-stage design will be used for statistical analysis. The primary goal of this study is determine the radiographic response rate. We will also characterize toxicity and determine if surrogate markers of tumor response and progression can be identified in patient serum, peripheral blood mononuclear cells (PBMC), and/or cerebrospinal fluid (CSF). To date, 4 pediatric subjects (ages 2-15) with recurrent low-grade gliomas have enrolled in the study. Poly-ICLC therapy has been well tolerated and none of the subjects have shown radiologic or clinical progressive disease. These results suggest that poly-ICLC may have a beneficial role in children with low-grade gliomas while minimizing treatment side effects. We have begun analyzing blood and CSF samples to attempt biomarker identification and correlation with subject responses, in hopes to yield a basis towards stratification and personalized therapy with recurrent disease.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2489. doi:1538-7445.AM2012-2489