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

This will be an open-label, Phase 1/2a, multicenter, single-arm, interventional trial that will first evaluate the dose limiting toxicity (DLT) of escalating numbers of ultrasound beams at constant acoustic pressure using a standard escalation (Phase 1) and then confirm the safety and efficacy of BBB opening (Phase 2a expansion).

Key Inclusion Criteria:

• Age ≥ 18 years, able and willing to give signed and informed consent.
• Patient with histologically proven recurrent de novo GBM:

• After at least a first-line standard of care (maximal safe resection, if feasible, radiation with temozolomide [TMZ], then TMZ);
• Any recurrence;
• Bevacizumab-naïve.*
• Patient eligible for carboplatin-based chemotherapy.
• Patient eligible for a surgical resection.
• Maximal tumor diameter at inclusion (pre surgery) ≤ 70 mm in T1wMRI.
• Patients should be stable, without evidence of a midline shift, significant peritumoral edema, or rapid progression of clinical symptoms.
• Karnofsky performance status ≥ 70.
• Patient receiving prednisone dose ≤ 40 mg (dexamethasone ≤ 6 mg) for at least 7 days.

Key Exclusion Criteria:

• Multifocal tumor (unless all localized in a 70 mm diameter area).
• Patients at risk of surgery site infection (2 or more previous craniotomies, neurosurgery within the last 3 months, poor skin condition, and/or previously infected surgical field).
• Posterior fossa tumor.
• Uncontrolled epilepsy.
• Patients with evidence of uncontrolled intracranial pressure.
• Patients with known intracranial aneurism or having presented intra-tumor spontaneous hemorrhage.
• Patients with coils, clips, shunts, intravascular stents, and/or unremovable wafer, non resorbable dura substitute, or reservoirs.
• Patients with medical need to continue antiplatelet therapy.
• Patients with known or suspected active or chronic infections.