PNOC021 Phase I Trial Evaluating the Combination of Trametinib and Everolimus in Pediatric and Young Adult Patients with Recurrent Gliomas

Award: $300,000 over 2 years (2020 – 2022)
Principal Investigators: Dr. Lindsay Kilburn, Children’s National Hospital, Dr. Angela Waanders, Lurie Children’s Hospital of Chicago, Dr. Mohamed AbdelBaki, Nationwide Children’s Hospital

Although preclinical and clinical data support the use of single agent MEK or mTOR inhibitors in the treatment of pediatric LGGs, there are anecdotal reports of tumor progression or rapid regrowth following cessation of therapy. Development of tumor resistance to single-targeted agents is inevitable, one mechanism being upregulation of parallel pathways. [10] Both preclinical and clinical studies have demonstrated additive or synergistic responses to therapy with trametinib and other MEK inhibitors when used in combination with both targeted and conventional chemotherapeutics. Therefore, further evaluation of rationale combination therapies is indicated in pediatric patients with gliomas, which may provide improved efficacy and or durability of response in these patients. Given the available preclinical data suggesting synergy with the combination of MEK and mTOR inhibition as well as demonstrated safety and efficacy of trametinib and everolimus in children with LGGs, we are proposing to evaluate the combination of trametinib and everolimus in children with recurrent or refractory LGGs.