PDCT-12. A PHASE I TRIAL OF TUMOR TREATING FIELDS WITH AND WITHOUT CONCOMITANT TEMOZOLOMIDE AND BEVACIZUMAB IN PEDIATRIC PATIENTS WITH HIGH-GRADE GLIOMA AND EPENDYMOMA

Abstract

High-grade gliomas (HGG) comprise 8-12% of brain tumors in children and include anaplastic astrocytoma or glioblastoma multiforme (GBM) pathology. Ependymoma is the third most common pediatric brain tumor accounting for 5-10% of all diagnoses. Treatment for these tumors involves surgical resection, adjuvant radiation and chemotherapy. The prognosis for high-grade glioma and recurrent ependymoma is poor and new therapies must be investigated to improve clinical outcomes for these patient populations. Tumor treating Fields (TTFs) is a non-invasive antimitotic treatment comprised of low-intensity alternating electric currents delivered through the Optune device approved for adults with GBM. This phase 1 study [NCT03128047] will include 2 cohorts of pediatric patients (N= 6-12), age >=1 and <18 years, with histologically-confirmed supratentorial newly-diagnosed or recurrent HGG and recurrent ependymoma. This study will have two safety endpoints to assess the safety and tolerability of TTFs for the treatment of pediatric HGG and ependymoma both alone and in combination with temozolomide (TMZ) and bevacizumab (BEV). Cohort 1 patients with recurrent HGG or ependymoma will receive TTFs (200 kHz 18 hours/ day). Cohort 2 patients with newly-diagnosed or recurrent HGG or recurrent ependymoma will receive TTFs plus BEV 10 mg/kg/dose and TMZ 200 mg/ m2/day. Safety endpoints will be determined by a standard 3 + 3 phase I study design based on the incidence and severity of adverse events and toxicities (CTCAE V4). There are no primary efficacy endpoints for this study. Patients will be followed to assess their progression-free and overall survival as the efficacy data gained from this study may be useful in designing future phase II/III investigations. The sample size will be determined by the number of observed severe adverse events related to therapy. A minimum of two and a maximum of twelve patients will be needed to complete this study.