A Phase 1/2 interventional study of SONOCLOUD and Nivolumab Injection in Melanoma and Metastatic Melanoma, sponsored by Assistance Publique - Hôpitaux de Paris. Status unknown at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-08-20.
Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 1/2, Interventional, and Treatment
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.
3,005 studies on the registry are indexed under Melanoma; 519 are open to participants now.
This study's planned enrollment of 21 is below the median of 38 across 2,350 interventional studies indexed under Melanoma.
Browse Melanoma studies →Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,505 studies on the registry; 1,006 are open to participants now.
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SonoCloud® is an active implantable device (implantation duration until 16 weeks at maximum after inclusion). SonoCloud® delivers low intensity pulsed UltraSound (US). Along with systemic injection of an US resonator, SonoCloud® demonstrated safe and efficient at repetitively opening the BBB.
Device: SONOCLOUD · Drug: Nivolumab Injection
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).
Nivolumab (flat dose: 240mg, 30 minutes infusion)
Most Successful Dose (MSD)
Dose with the highest probability of BBB opening efficacy without toxicity directly related to the ultrasound emission. Toxicity evaluation: Safety will be assessed clinically and using brain Magnetic resonance imaging (MRI). An electroencephalogram will be performed only if clinically needed. Dose-Limiting-Toxicities (DLTs) evaluation will be done during the first 4 weeks of treatment for Nivolumab treatment and 6 weeks for Nivolumab + Ipilimumab treatment. DLTs directly related to the ultrasound emission are defined as occurrence of an adverse effect during the first administration of treatment, such as: : * neurological deficit within 2 days after the procedure and persistent at day 15; * localized brain edema not preexisting to the procedure; * occurrence of cerebral median line deviation not controlled by routine treatment or requiring salvage surgical procedure; * partial epilepsy induced or enhanced after the procedure and not control
Time frame: Week 6
Best overall response rate, M3
Best clinical objective response (BOR) (defined with the Response assessment in neuro-oncology criteria (RANO) and immunotherapy response assessment for neuro-oncology (iRANO) and the response evaluation criteria in solid tumours (RECIST) version 1.1 and the Immune-Related Response Criteria during the 3 first months RANO : Wen, Patrick Y., et al. "Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group." J Clin Oncol 28.11 (2010): 1963-1972. iRANO : Okada, Hideho, et al. "Immunotherapy response assessment in neuro-oncology: a report of the RANO working group." The Lancet Oncology 16.15 (2015): e534-e542.
Time frame: Month 3
Overall response rate, M3
Clinical objective response (defined with the RANO and iRANO and the RECIST version 1.1 and the Immune-Related Response Criteria) during the 3 first months
Time frame: Month 3
Best intracranial overall response rate (BICORR), M3
Clinical efficacy will be assessed using TEP/TDM Scans (extracranial lesions) and MRI (intracranial metastases) at Month 3
Time frame: Month 3
Intracranial overall response rate (ICORR), M3
Clinical efficacy will be assessed using TEP/TDM Scans (extracranial lesions) and MRI (intracranial metastases) at Month 3
Time frame: Month 3
Best extracranial overall response rate (BECORR), M3
Best clinical objective response rate not taking account BICORR
Time frame: Month 3
Extracranial overall response rate (BECORR), M3
Clinical objective response not taking account ICORR
Time frame: Month 3
Plan to share: Undecided
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Assistance Publique - Hôpitaux de Paris