Safety and Efficacy of Sonocloud Device Combined With Nivolumab in Brain Metastases From Patients With Melanoma (SONIMEL01)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04021420|
Recruitment Status : Recruiting
First Posted : July 16, 2019
Last Update Posted : August 20, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Melanoma Metastatic Melanoma||Device: SONOCLOUD Drug: Nivolumab Injection||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||October 24, 2019|
|Estimated Primary Completion Date :||January 1, 2022|
|Estimated Study Completion Date :||July 5, 2023|
Experimental: low intensity pulsed UltraSound
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.
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 :
Drug: Nivolumab Injection
Nivolumab (flat dose: 240mg, 30 minutes infusion)
- Most Successful Dose (MSD) [ Time Frame: Week 6 ]
Dose with the highest probability of BBB opening efficacy without toxicity directly related to the ultrasound emission.
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
- Best overall response rate, M3 [ Time Frame: Month 3 ]
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.
- Overall response rate, M3 [ Time Frame: Month 3 ]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
- Best intracranial overall response rate (BICORR), M3 [ Time Frame: Month 3 ]Clinical efficacy will be assessed using TEP/TDM Scans (extracranial lesions) and MRI (intracranial metastases) at Month 3
- Intracranial overall response rate (ICORR), M3 [ Time Frame: Month 3 ]Clinical efficacy will be assessed using TEP/TDM Scans (extracranial lesions) and MRI (intracranial metastases) at Month 3
- Best extracranial overall response rate (BECORR), M3 [ Time Frame: Month 3 ]Best clinical objective response rate not taking account BICORR
- Extracranial overall response rate (BECORR), M3 [ Time Frame: Month 3 ]Clinical objective response not taking account ICORR
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04021420
|Contact: LEBBE Celeste, MD, PhD||142494679 ext +email@example.com|
|Contact: Matthieu RESCHE-RIGON, MD PhD||142499742 ext +firstname.lastname@example.org|