Safety and preliminary efficacy data from a phase I study of an implantable low intensity pulsed ultrasound (LIPU) device for disrupting the blood-brain barrier (BBB) in patients treated by chemotherapy for recurrent glioblastoma (GBM).

2016Background: The BBB limits the efficacy of many chemotherapies in GBM patients by blocking the passage of drugs to the brain. Two to four minutes of LIPU in combination with injection of micron-sized microbubblescan transiently disrupt the BBB to increase the passage of drugs such as carboplatin. Methods: This first-in-man, single arm, monocentric trial was performed at Hopital Universitaire Pitie-Salpetriere, Paris, France from 2014-2018. Recurrent GBM patients were implanted with (1) or (3) 1 MHz, 10-mm diameter cranial devices in burr holes during debulkingsurgery or during a dedicated procedure under local anesthesia. Ultrasound dose was escalated using a Simon titration design. The device was activated monthly to transiently disrupt the BBB before IV administration of carboplatin(AUC4-6). BBB disruption was visualized using MRI and patients were monitored clinically. Results: Twenty-seven patients were implanted with LIPU devices and 25 per-protocol were sonicated: 19 patients with (1) US emit...