RecruitingPhase 1NCT05293197
Safety Study of the Repeated Opening of the Blood-brain Barrier With the SonoCloud® Device to Treat Malignant Brain Tumors in Pediatric Patients
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
Sponsor
Assistance Publique - Hôpitaux de Paris
Enrollment
24 participants
Start Date
Feb 6, 2023
Study Type
INTERVENTIONAL
Conditions
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.
Eligibility
Min Age: 5 YearsMax Age: 17 Years
Inclusion Criteria18
- 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 Criteria43
- 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
- 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
Interventions
DEVICESonoCloud® (9 transducers)
SonoCloud®, sonication: dose escalation 6 cycles of sonication
Locations(3)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT05293197
Related Trials
Dual-Targeting CAR-NK Cells for Recurrent/Progressive Glioblastoma and High-Grade Glioma
NCT074809411 location
Panitumumab-IRDye800 in Diagnosing Participants With Malignant Glioma Undergoing Surgery
NCT035102081 location
CARv3-TEAM-E T Cells in Glioblastoma
NCT056603691 location
Mapping of Electrical Properties in the Brain
NCT064707111 location
NeuroPathways Intervention for Brain Tumor Patients
NCT059764901 location