Temporary disruption of the blood-brain barrier using an implantable ultrasound system for recurrent glioblastoma patients under IV carboplatin chemotherapy: initial phase 1/2a clinical trial observations

Alexandre Carpentier,Delphine Leclercq,Jean-Yves Delattre,Lauriane Goldwirt,Alexandre Vignot,Ahmed Idbaih,Catherine Horodyckid,Michael Canney,Jean-Yves Chapelon

doi:10.1186/2050-5736-3-s1-o14

Abstract

One of the main limitations to the efficacy of chemotherapy in the brain is the blood-brain barrier (BBB). Previous pre-clinical studies have demonstrated that disruption of the BBB using pulsed ultrasound in combination with an ultrasound microbubble contrast agent can significantly increase the concentration of chemotherapy agents in the brain. Our group has developed an implantable, MR compatible ultrasound device for temporarily disrupting the BBB. The safety of repeated disruption of the BBB using such a device was previously demonstrated in a long-term safety study in four non-human primates. The purpose of this work was to determine the safety and potential efficacy of temporarily disrupting the BBB in patients with recurrent glioblastoma before chemotherapy administration in a first-in-man clinical trial.

Highlights

Background/introduction One of the main limitations to the efficacy of chemotherapy in the brain is the blood-brain barrier (BBB)
Previous pre-clinical studies have demonstrated that disruption of the BBB using pulsed ultrasound in combination with an ultrasound microbubble contrast agent can significantly increase the concentration of chemotherapy agents in the brain
The safety of repeated disruption of the BBB using such a device was previously demonstrated in a long-term safety study in four non-human primates

Summary

Introduction

Background/introduction One of the main limitations to the efficacy of chemotherapy in the brain is the blood-brain barrier (BBB). Previous pre-clinical studies have demonstrated that disruption of the BBB using pulsed ultrasound in combination with an ultrasound microbubble contrast agent can significantly increase the concentration of chemotherapy agents in the brain. Our group has developed an implantable, MR compatible ultrasound device for temporarily disrupting the BBB. The safety of repeated disruption of the BBB using such a device was previously demonstrated in a long-term safety study in four non-human primates. The purpose of this work was to determine the safety and potential efficacy of temporarily disrupting the BBB in patients with recurrent glioblastoma before chemotherapy administration in a first-in-man clinical trial

Objectives

Methods

Results