PNOC 001:Phase II Study of Everolimus for Recurrent or Progressive Low-Grade Glioma in Children

This proposal fills a critical unmet need for a pediatric population with few other therapeutic alternatives and addresses an important problem in PLGG therapy, namely, how to best target dysregulated components within signaling pathways. This study (PNOC001) will elucidate mechanisms by which the most common genetic aberrations in PLGGs influence responses to novel, promising, translatable agents and will enable the next generation of clinical trials in which rational drug combinations are administered to appropriate patients in hypothesis-driven studies. This proposal steps beyond the usual approach of testing agents empirically in response-based trials. It utilizes a novel clinical trial statistical design to establish if specific molecular features are predictive markers of response to a targeted agent and establishes a new paradigm for PLGGs in which tumor tissue is acquired from each child in order to identify biomarkers of response. Funding support for the trial provides for the trial’s implementation and continued patient accrual across PNOC’s 15 member clinical trial consortium. Funding for the trial by PLGA fund at PBTF thus supports the robust accrual into an important clinical trial and enables children from all areas of the country to have access to a novel, directed treatment for PLGGs.

Funded in 2013.