Using ultrasound to open the blood-brain barrier for treating brain tumors in children
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
This study is testing if a special ultrasound device can safely help deliver chemotherapy directly to brain tumors in children to improve their treatment.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 24 (estimated) |
| Ages | 5 Years to 17 Years |
| Sex | All |
| Sponsor | Assistance Publique - Hôpitaux de Paris Academic / other |
| Drugs / interventions | bevacizumab, chemotherapy |
| Locations | 3 sites (Paris and 2 other locations) |
| Trial ID | NCT05293197 on ClinicalTrials.gov |
What this trial studies
This study aims to evaluate the safety and feasibility of using the SonoCloud device to open the blood-brain barrier (BBB) in pediatric patients with recurrent malignant brain tumors. By applying low intensity pulsed ultrasound, the study seeks to enhance the delivery of carboplatin chemotherapy directly to the tumor site. The SonoCloud device is implantable, MRI-compatible, and designed for repeated use, allowing for controlled and ambulatory treatments. The study builds on previous findings that suggest ultrasound can improve drug distribution in the brain and potentially increase survival rates in affected children.
Who should consider this trial
Good fit: Ideal candidates are pediatric patients aged 5 to 17 with recurrent malignant supra-tentorial brain tumors who are eligible for carboplatin treatment.
Not a fit: Patients with uncontrolled intracranial hypertension or those who cannot undergo MRI without sedation may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly improve treatment outcomes and survival rates for children with malignant brain tumors.
How similar studies have performed: Previous studies in adults have shown the feasibility and safety of this ultrasound technique, indicating potential for success in pediatric applications.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 * 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. Exclusion Criteria: * 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 * 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
Where this trial is running
Paris and 2 other locations
- Institut Curie — Paris, France (Recruiting)
- Service de neurochirugie Pédiatrique - Hôpital Necker- Enfants Malades — Paris, France (Recruiting)
- Institut Gustave Roussy — Villejuif, France (Recruiting)
Study contacts
- Principal investigator: Kevin BECCARIA, MD, PhD — Assistance Publique - Hôpitaux de Paris
- Study coordinator: Kevin BECCARIA, MD, PhD
- Email: kevin.beccaria@aphp.fr
- Phone: +33 1 71 39 65 92
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.