MelanomaPhase 1/2SONIMEL01NCT04021420
Safety and Efficacy of Sonocloud Device Combined With Nivolumab in Brain Metastases From Patients With Melanoma
A Phase 1/2 study testing SONOCLOUD and Nivolumab Injection in people with Melanoma and Metastatic Melanoma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Metastatic Melanoma
- What is being tested?
- SONOCLOUD and Nivolumab Injection
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteFrance
- Study dates
- 24 Oct 2019to 5 Jul 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with histologically confirmed metastatic melanoma
- Patients must have recovered from all side effects of their most recent systemic or local treatment for metastatic melanoma (grade ≤ 1).
- At least one measurable brain metastasis between 5 mm and 35 mm in diameter, not previously treated with surgery and/or radiosurgery and located less than 5 cm from the skull
- Patients may have received -or not- prior radiosurgery and/or surgery for brain metastases; if they have received prior local treatment, they must have at least 1new RANO and RECIST assessable brain metastases.
- BRAF status wild type or mutated (and in that case previous treatment with BRAF inhibitor and MEK inhibitor allowed)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1.
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- Age >18 year
- Hemoglobin ≥10g/dl
- Platelets ≥ 100000mm3
- Neutrophils ≥1500/mm3
- Creatinine Clearance ≥ 50ml/mn
- AST <3N
- ALT<3N
- Total bilirubin <1.5N
- Alkaline phosphatase <3N
- INR < 1.5
- Prothrombin ≥70%
- TCA <1.2
- No Hepatocellular insufficiency
- No unhealed wound on the head
- No allergy to poly isoprene
- Signed informed consent
- Patient with health insurance coverage
- Life expectancy > 3 months
Who cannot join
- Patient previously treated by antiPD1 (except adjuvant antiPD1 therapy)
- Ocular melanoma
- Symptomatic or diffuse leptomeningeal involvement.
- Symptomatic hemorrhagic brain metastases.
- Symptoms of incoercible intracranial pressure; patients receiving corticosteroids and patients presenting intermittent seizures can be enrolled if they have a stable dose of corticosteroids (≤ 30mg/day corticotherapy) and anti-epileptic treatment since at least 2 weeks before enrolment.
- Indication for urgent neurosurgery or radiotherapy
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- Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured or stage I untreated Chronic Lymphoid Leukemia.
- Known human immunodeficiency viruses (HIV) infection and any ongoing infectious disease or significant background.
- Concurrent administration of any anticancer therapies other than those administered in this study.
- Treatment with any cytotoxic and/or investigational drug, antiCTLA4 or targeted therapy ≤ 4 weeks or <5 half lives for targeted therapies or chemotherapy, prior to day 1 of study.
- Prior whole brain radiotherapy
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Saint-Louis Hospital
Paris, 75010
Celeste LEBBE, MD-PHD, 142494679 ext. +33, celeste.lebbe@aphp.fr
El-Mountacer el-abbassi, 142499742 ext. +33, el-abbassi.el-mountacer@univ-paris-diderot.fr
About this study
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
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
- Being tested
- SONOCLOUD, Nivolumab Injection
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SONOCLOUDDevice
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 :
- an implantable ultrasound transducer,
- a needle connection device,
- an external radiofrequency generator, and
- 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 InjectionDrug
Nivolumab (flat dose: 240mg, 30 minutes infusion)
| Study group | Role | What they receive |
|---|---|---|
| low intensity pulsed UltraSound | Experimental | 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. Receives: Device: SONOCLOUD; Drug: Nivolumab Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Week 6
Secondary outcomes (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.
Measured: 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
Measured: 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
Measured: 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
Measured: Month 3
Best extracranial overall response rate (BECORR), M3
Best clinical objective response rate not taking account BICORR
Measured: Month 3
Extracranial overall response rate (BECORR), M3
Clinical objective response not taking account ICORR
Measured: Month 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2019
- Study start24 Oct 2019
- Primary completion1 Jan 2022 (estimated)
- Study completion5 Jul 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04021420
- Sponsor's protocol ID
- P160950J
- Acronym
- SONIMEL01
- Status last verified
- Aug 2020
- First submitted
- 1 Jul 2019
- Last updated
- 20 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04021420
- Acronym / sponsor ID
- SONIMEL01 / P160950J
- Conditions
- Melanoma, Metastatic Melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 24 Oct 2019 (actual)
- Primary completion
- 1 Jan 2022 (estimated)
- Study completion
- 5 Jul 2023 (estimated)
- First posted
- 16 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| low intensity pulsed UltraSound | Experimental | Device: SONOCLOUD, Drug: Nivolumab InjectionSonoCloud® 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Patients with histologically confirmed metastatic melanoma
- Patients must have recovered from all side effects of their most recent systemic or local treatment for metastatic melanoma (grade ≤ 1).
- At least one measurable brain metastasis between 5 mm and 35 mm in diameter, not previously treated with surgery and/or radiosurgery and located less than 5 cm from the skull
- Patients may have received -or not- prior radiosurgery and/or surgery for brain metastases; if they have received prior local treatment, they must have at least 1new RANO and RECIST assessable brain metastases.
- BRAF status wild type or mutated (and in that case previous treatment with BRAF inhibitor and MEK inhibitor allowed)
Key exclusion criteria (11 listed)
- Patient previously treated by antiPD1 (except adjuvant antiPD1 therapy)
- Ocular melanoma
- Symptomatic or diffuse leptomeningeal involvement.
- Symptomatic hemorrhagic brain metastases.
- Symptoms of incoercible intracranial pressure; patients receiving corticosteroids and patients presenting intermittent seizures can be enrolled if they have a stable dose of corticosteroids (≤ 30mg/day corticotherapy) and anti-epileptic treatment since at least 2 weeks before enrolment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SONOCLOUDThe 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). | Device | low intensity pulsed UltraSound |
| Nivolumab InjectionNivolumab (flat dose: 240mg, 30 minutes infusion) | Drug | low intensity pulsed UltraSound |
Primary outcome
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. 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
6 secondary outcomes
Best overall response rate, M3
Time frame: Month 3
Overall response rate, M3
Time frame: Month 3
Best intracranial overall response rate (BICORR), M3
Time frame: Month 3
Intracranial overall response rate (ICORR), M3
Time frame: Month 3
Best extracranial overall response rate (BECORR), M3
Time frame: Month 3
Extracranial overall response rate (BECORR), M3
Time frame: Month 3
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2020.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SONOCLOUD and Nivolumab Injection in people with Melanoma and Metastatic Melanoma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact LEBBE Celeste, MD, PhD (142494679 ext. +33, celeste.lebbe@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Most Successful Dose (MSD) (time frame: Week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2020.