CTNI-29. SAFETY AND FEASIBILITY OF RHENIUM-186 NANOLIPOSOME (186RNL) IN RECURRENT GLIOMA: THE RESPECT™ PHASE 1 TRIAL

Abstract

Abstract BACKGROUND Liposomal rhenium-186 (186RNL) is a potent source of beta particles with short path length, variable dose rate, high radiation density and gamma emission. Preclinically, 186RNL delivered via convection enhanced delivery (CED) achieves very high doses of targeted radiation with a wide therapeutic index. We report the results of ReSPECT, the first in man, dose escalation phase 1 trial of 186RNL in recurrent glioma. METHODS Following computer assisted treatment planning and placement of intracranial catheter(s), we performed a single administration of 186RNL by CED. We obtained whole body planar and SPECT/CT imaging on days 1-8 following treatment for dosimetry and distribution and followed patients for safety, progression and survival. RESULTS Twenty-one patients across 7 cohorts received 1.0-22.3mCi in a volume of 0.6-8.80mL. Mean tumor volume was 8.3mL (0.9-22.8mL). Patients had a mean of 1.7 recurrences, 5 received prior bevacizumab. Overall, 19/21 patients and all after cohort 4 had grade 4 glioma (glioblastoma). We used a CED rate of 5-20µl/min per catheter, with 1-4 catheters used per patient. Mean absorbed radiation dose to the tumor was 255Gy (8.9-740Gy) while exposure outside the brain was negligible. The mean percentage tumor in the treated volume (Tu/Tv) was 60.3% (19.8%-100%). Thus far, we have observed no dose limiting toxicities, one grade 3 treatment related adverse event (AEs), and the majority of AEs were mild in intensity. The incidence and severity of AEs did not correlate with increasing dose. Mean Tu/Tv in patients not receiving prior bevacizumab was 75% vs. 48% in those that had. Thus far, overall survival (OS) in 16 bevacizumab naïve patients is 49 weeks with 7 (44%) patients still alive and a positive correlation of OS to Tu/Tv. CONCLUSIONS 186RNL achieves high absorbed doses without significant toxicity with favorable overall survival.