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Malignant Brain TumorPhase 1SONOKIDNCT05293197

Safety Study of the Repeated Opening of the Blood-brain Barrier With the SonoCloud® Device to Treat Malignant Brain Tumors in Pediatric Patients

A Phase 1 study testing SonoCloud® (9 transducers) in people with Malignant Brain Tumor and Malignant Glioma, run by Assistance Publique - Hôpitaux de Paris at 3 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Purpose : the aim of this study is to assess the feasibility and safety of ultrasound-induced opening of the blood-brain barrier (BBB) with the SonoCloud-9 implantable ultrasound device in pediatric patients treated for a recurrent malignant supra-tentorial brain tumor treated with carboplatin. Read more about this study

Who is it for?
Ages 5 to 17 years
What is being tested?
SonoCloud® (9 transducers)
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
3 sitesFrance
Study dates
6 Feb 2023to 1 Oct 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

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 5 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • patient aged ≥ 5 years old and < 18 years old
  • patient able to receive sonications and perform MRI studies without sedation
  • diagnosis of supra-tentorial primary malignant brain tumor (e.g. malignant glioma, embryonal tumor including ATRT, ependymoma)
  • recurrence or progression of brain tumor after at least a first line of standard treatment (multifocal tumors and metastatic disease allowed)
  • indication of treatment with carboplatin, validated in multidisciplinary meeting
  • Karnofsky performance scale index (patients ≥ 16 years old) or Lansky performance status (patients < 16 years old) > 50% (a patient with a performance status score altered by a motor deficit due to tumor infiltration will be allowed to be included)
Show all 18Show fewer
  • no threat of brain herniation or uncontrolled intracranial hypertension
  • corticosteroids treatment ≤ 1mg/kg/day
  • neutrophils > 1.5 x 109/L
  • platelets > 100 x 109/L
  • total bilirubin < 1.5x upper limit of normal, AST et ALT < 2.5x upper limit of normal
  • serum creatinin < 1.5x upper limit of normal for the age or creatinine clairance >70mL/min/1.73m2 (EDTA method or 24h urine)
  • coagulation parameters in the normal limits for age (fibrinogen, prothrombin time and activated clotting time)
  • no grade 2 or more toxicity depending on the NCI-CTCAE v5.0 criteria
  • no healed wound on the scalp
  • covered by health insurance
  • for patients of chilbearing age (15-17 years old) : a negative pregnancy test and an efficient method of birth control
  • written consent signed by the patient (if possible) and his parents or legal representatives.

Who cannot join

  • weight <15kg
  • significant intra-tumoral bleeding (hematoma) or ipsilateral subdural effusion
  • antineoplastic treatment other than carboplatin taken at the same time or stopped since less than:
  • 6 weeks for nitrosoureas
  • 1 month for temozolomide
  • 1 month for bevacizumab
Show all 43Show fewer
  • 5 half-lives for tyrosin kinase inhibitors
  • 3 weeks for any other chemotherapy
  • for the first sonication session
  • radiotherapy during the last 6 weeks
  • any other cancer treated during the last 5 years
  • any other uncontrolled disease or active infection
  • any other co-morbidity that could compromise participation to the study (in the judgement of the clinical investigator)
  • any anatomical particularity (skull thickness, thin skin) that could compromise a safe implantation of the device and/or compromise the quality of the treatment (in the judgement of the clinical investigator)
  • implanted defibrillator/pacemaker, neurostimulator, cochlear implant, intracerebral ferromagnetic vascular clip
  • any contraindication to general anesthesia
  • any contraindication to MRI or known allergy to gadolinium or other MRI contrast agent/
  • any contraindication to ultrasound contrast agent:
  • allergy to the active substance or any excipient
  • acute coronary syndrome or uncontrolled ischemic heart disease
  • chronic heart failure or history of acute heart failure or heart failure grade III or IV
  • treatment with dobutamine
  • severe pulmonary arterial hypertension
  • uncontrolled systemic hypertension
  • respiratory distress syndrome
  • carboplartin hypersensitivity
  • treatment with phenytoin or fosphenytoin
  • earlier vaccination with attenuated alive vaccine
  • diminished auditory acuity ≥ grade 3 on CTCAE classification
  • history of thermoregulation disorder
  • impossibility of a rigorous medical follow-up due to geographic, social or mental reasons
  • pregnant and lactating women
  • contemporaneous treatment by anticoagulant or platelet aggregation inhibiting drugs
  • contemporaneous treatment possibly toxic for the central nervous system. The following treatments are excluded if taken less than 5 half-lives before the ultrasound session (unknown toxicity in case of BBB disruption) :
  • benzodiazepine (or any sedative or hypnotique drug)
  • antihistamine
  • proconvulsant drugs
  • butyrophenone, phenothiazine, or any "conventional" antipsychotic drug
  • barbiturate
  • MAO inhibitor
  • anticholinergic
  • anticoagulant
  • any contemporaneous treatment that, in the judgement of the clinical investigator, could induce brain toxicity after BBB disruption

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Kevin BECCARIA, MD, PhD contact

+33 1 71 39 65 92

kevin.beccaria@aphp.fr

Nelly BRIAND, MD, PhD contact

+33 1 44 38 18 62

nelly.briand@aphp.fr

France3 sites, 3 recruiting

  • Institut Curie

    Paris, 75005

    Franck BOURDEAUT, MD, PhD, +33 1 4432 44 71, franck.bourdeaut@curie.fr

    Franck BOURDEAUT

    Recruiting

  • Service de neurochirugie Pédiatrique - Hôpital Necker- Enfants Malades

    Paris, 75015

    Kevin BECCARIA, MD, PhD, +33 1 71 39 65 92, kevin.beccaria@aphp.fr

    Kevin BECCARIA

    Recruiting

  • Institut Gustave Roussy

    Villejuif, 94800

    Jacques GRILL, MD, PhD, +33 142116209, jacques.grill@gustaveroussy.fr

    Jacques GRILL

    Recruiting

Other trials in France

About this study

Official title: Phase I Trial Assessing the Safety of the Repeated Ultrasound-induced Opening of the Blood-brain Barrier in Pediatric Patients With Refractory Supra-tentorial Malignant Brain Tumors Before Chemotherapy Administration

Purpose : the aim of this study is to assess the feasibility and safety of ultrasound-induced opening of the blood-brain barrier (BBB) with the SonoCloud-9 implantable ultrasound device in pediatric patients treated for a recurrent malignant supra-tentorial brain tumor treated with carboplatin.

Study hypothesis : the blood-brain barrier can be transiently and safely opened with pulsed low intensity ultrasound immediately prior to intravenously delivered chemotherapy. The opening of the BBB with the SonoCloud-9 system will increase the tumor exposure to carboplatin and increase progression-free and overall survival in pediatric patients treated for a recurrent malignant supra-tentorial brain tumor.

Read the detailed description

Malignant brain tumors are the first cause of death by cancer in children and adolescents. The dismal prognosis of malignant brain tumors is partially due to the existence of the blood brain barrier (BBB), a physiological barrier that limits the penetration of almost all molecules from the blood stream to the brain, including antineoplastic drugs.

It has been shown that the application of low intensity ultrasound on the brain in association with intravenous microbubbles leads to transient and safe opening of the BBB. Many preclinical studies have demonstrated that ultrasound-induced opening of the BBB increases the distribution of therapeutic molecules into the brain and allows tumor control and increases survival in animal models (mice, rabbits, pigs, primates).

An innovative implantable ultrasound system, the SonoCloud device, has been developed in order to repeatedly open the BBB in synchronization with chemotherapy protocols.

This intracranial and subcutaneous device is not visible and MRI compatible and allows repeatable and ambulatory treatments. Moreover, such a device allows the delivery of low intensity ultrasound in a controlled and reproductible manner.

A phase I/IIa trial has confirmed the feasibility and safety of this technique in adult patients treated for recurrent glioblastoma with carboplatin-based chemotherapy.

This study will assess the feasibility and safety of ultrasound-induced opening of the BBB with the SonoCloud device in pediatric patients treated with carboplatin chemotherapy for a recurrent supra-tentorial malignant brain tumor. The study will determine the maximum tolerated ultrasound acoustic pressure that can be used for BBB opening and the safety of the activation of 3, then 9 transducers with the SonoCloud-9® device. Patients will follow 6 months cycles of treatment. If the treatment is well tolerated, patients will be able to be treated for 6 more cycles.

The magnitude and intensity of the BBB opening, its clinical (overall survival) and radiological (progression-free survival) efficacy will be assessed as secondary endpoints. Safety of the ultrasound contrast agent SonoVue will also be evaluated in this indication in the pediatric population.

An ancillary study will assess circulating tumor DNA (ctDNA) concentrations in patients with recurrence of a supra-tentorial malignant brain tumor, at diagnosis and during repeated opening of the BBB. The study will assess the correlation between ctDNA concentrations and tumor evolution.

Being tested
SonoCloud® (9 transducers)
Keywords
Low intensity pulsed ultrasound (LIPU), Therapeutic ultrasound, Blood-brain barrier (BBB), Malignant brain tumor, Brain cancer, Carboplatin, Children, Adolescents
Medical subject headings
Brain Neoplasms, Glioma, Neoplasms, Germ Cell and Embryonal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SonoCloud® (9 transducers)Device

    SonoCloud®, sonication: dose escalation 6 cycles of sonication

Study groups in NCT05293197
Study groupRoleWhat they receive
SonoCloud®ExperimentalSonoCloud® : dose escalation 6 cycles of sonication
Receives: Device: SonoCloud® (9 transducers)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limiting toxicity directly linked to US emissions by the SonoCloud-9® (3 transducers)

    Clinical evaluation (neurological deficit, intracranial hypertension, epilepsy) during acoustic pressure dose escalation, after each sonication (48h)

    Measured: Monthly up to 12 months

  2. Dose limiting toxicity directly linked to US emissions by the SonoCloud-9®(3 transducers)

    Radiological evaluation (hemorrage, ischemia, brain swelling) during acoustic pressure dose escalation, after each sonication

    Measured: Monthly up to 12 months

Secondary outcomes (20)

  1. BBB opening intensity with the SonoCloud® device

    Grading of BBB disruption using the scale previously described (Carpentier et al 2016), after each sonication

    Measured: Monthly, up to 12 months

  2. Clinical efficacy of BBB disruption by the SonoCloud® device in association with systemic chemotherapy

    Overall Survival (OS)

    Measured: Month 3

  3. Clinical efficacy of BBB disruption by the SonoCloud® device in association with systemic chemotherapy

    Overall Survival (OS)

    Measured: Month 6

  4. Radiological efficacy of BBB disruption by the SonoCloud® device in association with systemic chemotherapy

    Progression Free Survival (PFS) using RANO Criteria

    Measured: Month 3

  5. Radiological efficacy of BBB disruption by the SonoCloud® device in association with systemic chemotherapy

    Progression Free Survival (PFS) using RANO Criteria

    Measured: Month 6

  6. Allergic adverse events related to ultrasound contrast agent SonoVue®

    Allergic reactions (cutaneous eruption, oedema, respiratory failure) in relation to the use of the ultrasound contrast agent SonoVue® for BBB disruption in the pediatric population, during and after each sonication

    Measured: Monthly, up to 12 months

  7. Cardiac adverse events related to ultrasound contrast agent SonoVue®

    Cardiac reactions (thoracic pain, cardiac failure, EKG modification) in relation with the use of the ultrasound contrast agent SonoVue® for BBB disruption in the pediatric population, during and after each sonication

    Measured: Monthly, up to 12 months

  8. Feasibility of the BBB disruption technique

    Complications associated with the implantation of the SonoCloud® device : acute pain evaluation using VAS (Visual Analogue Scale) for patients >_ 7 years old or using behavioral pain scale EVENDOL for patients <7 years old, immediately after implantation

    Measured: Monthly, up to 12 months

  9. Feasibility of the BBB disruption technique

    Complications associated with the implantation of the SonoCloud® device : acute pain evaluation using VAS (Visual Analogue Scale) for patients >_ 7 years old or using behavioral pain scale EVENDOL for patients <7 years old, at day 1 after implantation

    Measured: Monthly, up to 12 months

  10. Feasibility of the BBB disruption technique

    Complications associated with the implantation of the SonoCloud® device : chronic pain evaluation using VAS (Visual Analogue Scale) for patients >_7 years old or using behavioral pain scale EVENDOL for patients <7 years old, monthly, before each new cycle of treatment

    Measured: Monthly, up to 12 months

  11. Feasibility of the BBB disruption technique

    Complications associated with the implantation of the SonoCloud® device using radiological examination : device position and post-operative complication (hematoma), one day after implantation

    Measured: Day 1 after implantation

  12. Feasibility of the BBB disruption procedure

    Assessment of complications associated with the sonications : pain evaluation using VAS (Visual Analogue Scale) for patients >_ 7 years old or using behavioral pain scale EVENDOL for patients <7 years old at needle connexion

    Measured: Monthly, up to 12 months

  13. Feasibility of the BBB disruption procedure

    Complications associated with the implantation of the SonoCloud® device : pain evaluation using VAS (Visual Analogue Scale) for patients >_ 7 years old or using behavioral pain scale EVENDOL for patients <7 years old, during sonication

    Measured: Monthly, up to 12 months

  14. Skin complications relation to the BBB disruption procedure

    Assessment of skin complications associated with sonications : eschar and/or infection, before each cycle of treatment

    Measured: Monthly, up to 12 months

  15. Feasibility of the BBB disruption procedure

    Process evaluated by the surgeon: number of tests necessary for needle connexion to the device, at each sonication

    Measured: Monthly, up to 12 months

  16. Feasibility of the BBB disruption procedure

    Process evaluated by the surgeon : duration from needle connexion to the end of sonication, at each sonication

    Measured: Monthly, up to 12 months

  17. Feasibility of the BBB disruption procedure

    Process evaluated by the surgeon : duration for device implantation

    Measured: During surgery

  18. Biodisponibility of the SonoCloud-9® device

    Histological analysis of tissue around the device : thickness, inflammation, biocompatibility, at explantation

    Measured: 12 months

  19. Assessment of SonoCLOUD- 9® device resistance

    Physical analysis of the device, at explantation

    Measured: 12 months

  20. DNA and tumor cells concentrations in blood and cerebrospinal fluid

    Evaluation of the effect of BBB disruption with the SonoCloud-9® device on the circulation of tumoral components in the blood flow, at each cycle of treatment

    Measured: Monthly, up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Mar 2022
  2. Study start6 Feb 2023
  3. Primary completion1 Oct 2026 (estimated)
  4. Study completion1 Oct 2028 (estimated)

Resources

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05293197
Sponsor's protocol ID
D20181321
Other IDs
2021-002790-26
Acronym
SONOKID
Status last verified
Apr 2026
First submitted
9 Feb 2022
Last updated
6 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Carpentier A, Canney M, Vignot A, Reina V, Beccaria K, Horodyckid C, Karachi C, Leclercq D, Lafon C, Chapelon JY, Capelle L, Cornu P, Sanson M, Hoang-Xuan K, Delattre JY, Idbaih A. Clinical trial of blood-brain barrier disruption by pulsed ultrasound. Sci Transl Med. 2016 Jun 15;8(343):343re2. doi: 10.1126/scitranslmed.aaf6086.

    PubMed 27306666

  • Idbaih A, Canney M, Belin L, Desseaux C, Vignot A, Bouchoux G, Asquier N, Law-Ye B, Leclercq D, Bissery A, De Rycke Y, Trosch C, Capelle L, Sanson M, Hoang-Xuan K, Dehais C, Houillier C, Laigle-Donadey F, Mathon B, Andre A, Lafon C, Chapelon JY, Delattre JY, Carpentier A. Safety and Feasibility of Repeated and Transient Blood-Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma. Clin Cancer Res. 2019 Jul 1;25(13):3793-3801. doi: 10.1158/1078-0432.CCR-18-3643. Epub 2019 Mar 19.

    PubMed 30890548

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SonoCloud® (9 transducers) in people with Malignant Brain Tumor and Malignant Glioma, run by Assistance Publique - Hôpitaux de Paris at 3 sites 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 18 inclusion and 43 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: looking for participants now, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Kevin BECCARIA, MD, PhD (+33 1 71 39 65 92, kevin.beccaria@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicity directly linked to US emissions by the SonoCloud-9® (3 transducers) (time frame: Monthly up to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05293197, which also lists 2 linked publications.

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 6 May 2026.

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