💬In plain words
What the trial is, and whether it could suit you
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.
Sign in to get the eligibility rules as simple questions to take to your doctor.
📋 Eligibility rules (as published)
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