Informations générales (source: ClinicalTrials.gov)
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
Interventional
Phase 1
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
février 2023
octobre 2027
11 septembre 2025
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.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Necker-Enfants Malades | Kevin BECCARIA, MD, PhD | jeudi 11 septembre 2025 | Contact (sur clinicalTrials) | ||
| CLCC INSTITUT CURIE | Franck BOURDEAUT, MD, PhD | jeudi 11 septembre 2025 | Contact (sur clinicalTrials) | ||
| CLCC INSTITUT GUSTAVE ROUSSY | Jacques GRILL, MD, PhD | jeudi 11 septembre 2025 | Contact (sur clinicalTrials) | ||
Critères
Tous
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.
- 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.
- 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