CTNI-37. REPEATED OPENING OF THE BLOOD-BRAIN BARRIER WITH THE SKULL-IMPLANTABLE SONOCLOUD-9 (SC9) DEVICE: PHASE 1 TRIAL OF NAB-PACLITAXEL AND SC9 IN RECURRENT GLIOBLASTOMA

Abstract BACKGROUND The blood-brain barrier (BBB) is a major impediment to pharmacological treatment of gliomas. Low-intensity pulsed ultrasound with concomitant administration intravenous microbubbles (LIPU/MB), temporarily opens the BBB. Here we investigate pharmacokinetics and safety this approach repeated delivery albumin-bound paclitaxel (Abraxane®, ABX) peri-tumoral brain. To perform LIPU/MB-based BBB opening prior ABX infusions, used novel 6 x cm device 9 emitters (SC9) that implanted in skull window after tumor resection. METHODS A Phase 1 dose-escalation trial using Bayesian adaptive design was conducted (NCT04528680). Patients recurrent operable glioblastoma, WHO PS ≤ 2 adequate bone marrow organ function were eligible. After resection implantation SC9, cycles by LIPU/MB immediately followed ABX, performed every 3 weeks. Intraoperative low dose given allowed for investigation tissue concentrations pharmacokinetics. RESULTS Seventeen patients have been treated at six escalating levels (40-260 mg/m2). At 260 mg/m2, grade reversible taxane-associated limiting encephalopathy observed one patient. patient continued lower subsequent cycles. second exhibited on cycle 2. One developed cumulative peripheral neuropathy. pharmacokinetic studies showed non-enhancing brain increased 3.7-fold LIPU/MB. sc-RNA-sequencing transcriptional dysregulation membrane transporters, pathways related trans-cytosis as well cell-cell cell-matrix adhesion. CONCLUSIONS skull-implantable enhances penetration large regions procedure can be repeatedly safely. LIPU-based leads alterations endothelium. Funding: NIH/NCI 1R01CA245969-01A1, CarThera (SC9 devices), BMS/Celgene (Abraxane®).