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

This is an open label study of everolimus in children with recurrent or progressive low-grade glioma. All patients will receive everolimus at a dose of 5 mg/m2/dose daily. An adaptive Simon two-stage design for phase 2 studies of targeted therapies will be used to assess the efficacy primary objective. The proposed treatment with everolimus will be deemed not worthy of further investigation in this patient population if the true PFS at 6-months (PFS6) is less than 50%. If in the first stage, with a combined sample size of 25, there is preliminary evidence to suggest efficacy of everolimus is restricted to patients with PI3K/AKT/mTOR activation as measured by p-S6 positivity, a total of 45 patients will be enrolled and the design will have 81% statistical power to detect a true disease stabilization rate ≥70%. If in the first stage there is preliminary evidence to suggest efficacy of everolimus is independent of PI3K/AKT/mTOR activation, a total of 65 patients will be enrolled and the design will have \>95% statistical power to detect a true disease stabilization rate ≥70%.