NCT04021420

Safety and Efficacy of Sonocloud Device Combined With Nivolumab in Brain Metastases From Patients With Melanoma

Safety and Efficacy of Blood Brain Barrier Opening With Implantable Device Sonocloud® Combined With Nivolumab Used Alone or an Association With Ipilimumab in Brain Metastases From Patients With Malignant Melanoma

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 21 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Anti PD-1 monoclonal antibodies (nivolumab and pembrolizumab) alone or in association with antiCTLA4 (Ipilimumab) are established as indisputable treatment of metastatic melanoma, with unprecedented overall survival, and are indicated for first-line treatment including patients with BRAF mutation. Given their high molecular weight, their penetration in the brain sanctuary is uncertain and relies on disruption of the Blood Brain Barrier (BBB) which occurs occasionally. SonoCloud® is an implantable device delivering low intensity pulsed UltraSound (US). Along with systemic injection of an US resonator, SonoCloud® demonstrated safe and efficient at repetitively opening the BBB. The investigators anticipate that BBB opening could help at increasing brain penetration of monoclonal antibodies and potentially boosting immunity in the brain. This could translate in controlling brain disease with the same magnitude as for extra-cranial disease. This would also open avenues for optimizing the treatment of brain metastases in combination with checkpoint inhibitors in many other cancers.

Conditions

• Melanoma
• Metastatic Melanoma

Interventions

Type	Name	Description
DEVICE	SONOCLOUD	The SonoCloud System is an active implantable medical. The SonoCloud is indicated to locally and transiently increase the permeability of the blood brain barrier to facilitate the passage of substances into the cerebral parenchyma. The SonoCloud System consists of : 1. an implantable ultrasound transducer, 2. a needle connection device, 3. an external radiofrequency generator, and 4. an ultrasound resonator. The SonoCloud® is designed to be fixed to the skull. The device is placed in a burr hole or in place of a bone flap and ultrasound energy is delivered directly to the brain tissue, without traversing the skull bone. The device is activated by connecting the implant to the external generator system using the transdermal needle. Once connected to the external generator, the implant delivers low-intensity pulsed UltraSound (US) for duration of 120-270 seconds. A total of 3 US dose levels will be evaluated (0.78, 0.9 and 1.03 MPa).
DRUG	Nivolumab Injection	Nivolumab (flat dose: 240mg, 30 minutes infusion)

Timeline

• Start date: 2019-10-24
• Primary completion: 2022-01-01
• Completion: 2023-07-05
• First posted: 2019-07-16
• Last updated: 2020-08-20

Locations

1 site across 1 country: France