CTNI-19. A TWO-PART, PHASE 1 STUDY OF RHENIUM-186 NANOLIPOSOME (186RNL) DELIVERED BY CONVECTION ENHANCED DELIVERY (CED) FOR RECURRENT OR PROGRESSIVE CHILDHOOD EPENDYMOMA AND HIGH-GRADE GLIOMA (HGG)

Abstract

Abstract Childhood ependymoma and HGG are difficult tumors to treat. Recurrent ependymoma is treated with re-resection and multiple rounds of external beam radiation therapy (EBRT). HGG is treated with chemoradiation followed by clinical trials, if available. While EBRT remains a central component of management, it is limited by tolerance of the surrounding normal brain tissue. Rhenium-186 NanoLiposome (186RNL) permits the selective delivery of beta-emitting radiation with excellent tumor retention. In an adult Phase 1 trial for recurrent glioblastoma (NCT01906385), the mean absorbed dose to the tumor was 392 Gy (CI 306 – 478), markedly higher than absorbed doses typically delivered by EBRT. Despite this, no dose-limiting toxicity was observed and no treatment-related serious adverse events have occurred. Here, we describe the first pediatric trial using a two-part, Phase 1 dose-finding study followed by expansion cohorts to explore efficacy. Enrolling subjects will be 6 to 21 years of age with a diagnosis of recurrent ependymoma or HGG. Subjects will be allowed to enroll either if they have exhausted standard of care options or if they are clinically stable and surgical resection can be deferred by 4 weeks. Part 1 will enroll up to 24 subjects to determine the maximum feasible dose (MFD) of 186RNL administered by CED. Tumor size and concentration of infusate will be escalated in each cohort (A-D) to a maximum tumor diameter of 6 cm (114.1 mL) and a concentration of 2mCi/ml. Up to 4 CED catheters will be used. Part 2 will independently evaluate 186RNL in 2 different expansion cohorts: Cohort 2A: recurrent ependymoma; Cohort B: recurrent HGG. The primary endpoint for Cohort 2A is overall response rate (ORR) by Radiographic Assessment in Pediatric Neuro-Oncology (RAPNO) criteria and the primary endpoint for Cohort 2B is progression free survival. Planned enrollment will begin in early 2023.