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

NCT05293197 | Recruiting Phase 1 DMC

• 2 other identifiers: D201813212021-002790-26
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief 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. 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.

Conditions

Malignant Brain Tumor; Malignant Glioma; Embryonal Tumor

Keywords

Low intensity pulsed ultrasound (LIPU); Therapeutic ultrasound; Blood-brain barrier (BBB); Malignant brain tumor; Brain cancer; Carboplatin; Children; Adolescents

Outcome Measures

Primary Outcomes (2)

• 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)

  Monthly up to 12 months

• 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

  Monthly up to 12 months

Secondary Outcomes (20)

• BBB opening intensity with the SonoCloud® device

  Monthly, up to 12 months

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

  Month 3

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

  Month 6

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

  Month 3

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

  Month 6

Study Arms (1)

SonoCloud®

EXPERIMENTAL

SonoCloud® : dose escalation 6 cycles of sonication

Device: SonoCloud® (9 transducers)

Interventions

SonoCloud® (9 transducers) DEVICE

SonoCloud®, sonication: dose escalation 6 cycles of sonication

SonoCloud®

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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:
• weeks for nitrosoureas
• month for temozolomide
• month for bevacizumab
• half-lives for tyrosin kinase inhibitors
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• CarThera: collaborator
• Gustave Roussy, Cancer Campus, Grand Paris: collaborator
• Institut Curie: collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (3)

Institut Curie

Paris, 75005, France

RECRUITING

Service de neurochirugie Pédiatrique - Hôpital Necker- Enfants Malades

Paris, 75015, France

RECRUITING

Institut Gustave Roussy

Villejuif, 94800, France

RECRUITING

Related Publications (2)

• 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.

  PMID: 27306666 BACKGROUND

• 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.

  PMID: 30890548 BACKGROUND

MeSH Terms

Conditions

Brain Neoplasms; Glioma; Neoplasms, Germ Cell and Embryonal

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Kevin BECCARIA, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2022
• First Posted: March 24, 2022
• Study Start: February 6, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)