Safety and Efficacy of Transient Opening of the Blood-brain Barrier (BBB) With the SonoCloud-9

Summary

Recurrent glioblastoma (GBM) is a disease with high unmet clinical need. The standard of care for patients with GBM includes surgery, radiotherapy and chemotherapy. Despite this aggressive treatment, the overall median survival of patients with GBM remains at 15-20 months. In more than 95% of cases, tumor recurrence is observed within 2 cm to 3 cm of the resection cavity within 4-7 months after initial treatments. One of the main causes of recurrence is the inability of chemotherapies to enter the brain from the systemic circulation due to the blood-brain barrier (BBB). The BBB is unique to cerebral blood vessels and blocks most drugs from entering the brain in sufficient concentrations. The SonoCloud-9 (SC9) System delivers ultrasound to locally and transiently increase the permeability of the BBB to allow the passage of drugs into the cerebral parenchyma. The SC9 is dimensioned to cover the resection area and surrounding tissues in patients with recurrent GBM. The large sonicated volume covered by the SC9 device allows for broad BBB disruption and should allow for carboplatin chemotherapy to penetrate the surrounding tumor infiltrative area. By enhancing drug concentrations, it is hypothesized that further disease progression will be prevented.

Timeline

Start

2019-02-18

Primary completion

2021-06-23

Completion

2022-06-30

Outcome

Met primary endpoint

paper BBB opening endpoint was met with 90% of emitters showing BBB disruption on MRI after sonication. PMID 38396134 ↗

Publications

• Background Carpentier A, Canney M, Vignot A, Reina V, Beccaria K, Horodyckid C, Karachi C, Leclercq D, Lafon C, Chapelon JY, Capelle L, Cornu P, Sanson M, Hoang-Xuan K, Delattre JY, Idbaih A. Clinical trial of blood-brain barrier disruption by pulsed ultrasound. Sci Transl Med. 2016 Jun 15;8(343):343re2. doi: 10.1126/scitranslmed.aaf6086.
• Carpentier A, Stupp R, Sonabend AM, Dufour H, Chinot O, Mathon B, Ducray F, Guyotat J, Baize N, Menei P, de Groot J, Weinberg JS, Liu BP, Guemas E, Desseaux C, Schmitt C, Bouchoux G, Canney M, Idbaih A. Repeated blood-brain barrier opening with a nine-emitter implantable ultrasound device in combination with carboplatin in recurrent glioblastoma: a phase I/II clinical trial. Nat Commun. 2024 Feb 23;15(1):1650. doi: 10.1038/s41467-024-45818-7.
• Sonabend AM, Gould A, Amidei C, Ward R, Schmidt KA, Zhang DY, Gomez C, Bebawy JF, Liu BP, Bouchoux G, Desseaux C, Helenowski IB, Lukas RV, Dixit K, Kumthekar P, Arrieta VA, Lesniak MS, Carpentier A, Zhang H, Muzzio M, Canney M, Stupp R. Repeated blood-brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in patients with recurrent glioblastoma: a phase 1 trial. Lancet Oncol. 2023 May;24(5):509-522. doi: 10.1016/S1470-2045(23)00112-2.

Drugs

Indications