SULFUR HEXAFLUORIDE for Recurrent primary supratentorial malignant brain tumor

Inclusion criteria

• {"criterion_text":"- patient aged ≥ 5 years old and < 18 years old"}
• {"criterion_text":"- platelets > 100 x 109/L"}
• {"criterion_text":"- total bilirubin < 1.5x upper limit of normal, AST et ALT < 2.5x upper limit of normal"}
• {"criterion_text":"- serum creatinin < 1.5x upper limit of normal for the age or creatinine clairance >70mL/min/1.73m2 (EDTA method or 24h urine)"}
• {"criterion_text":"- coagulation parameters in the normal limits for age (fibrinogen, prothrombin time and activated clotting time)"}
• {"criterion_text":"- no grade 2 or more toxicity depending on the NCI-CTCAE v5.0 criteria"}
• {"criterion_text":"- no healed wound on the scalp"}
• {"criterion_text":"- covered by health insurance"}
• {"criterion_text":"- for patients of chilbearing age (15-17 years old) : a negative pregnancy test and an efficient method of birth control"}
• {"criterion_text":"- written consent signed by the patient (if possible) and his parents or legal representatives."}
• {"criterion_text":"- patient able to receive sonications and perform MRI studies without sedation"}
• {"criterion_text":"- diagnosis of supra-tentorial primary malignant brain tumor (e.g. malignant glioma, embryonal tumor including ATRT, ependymoma)"}
• {"criterion_text":"- recurrence or progression of brain tumor after at least a first line of standard treatment (multifocal tumors and metastatic disease allowed)"}
• {"criterion_text":"- indication of treatment with carboplatin, validated in multidisciplinary meeting"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- no threat of brain herniation or uncontrolled intracranial hypertension"}
• {"criterion_text":"- corticosteroids treatment ≤ 1mg/kg/day stable for the last 7 days"}
• {"criterion_text":"- neutrophils > 1.5 x 109/L"}

Exclusion criteria

• {"criterion_text":"- weight <15kg"}
• {"criterion_text":"- any contraindication to general anesthesia"}
• {"criterion_text":"- any contraindication to MRI or known allergy to gadolinium or other MRI contrast agent/"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- carboplartin hypersensitivity"}
• {"criterion_text":"- treatment with phenytoin or fosphenytoin"}
• {"criterion_text":"- earlier vaccination with attenuated alive vaccine"}
• {"criterion_text":"- diminished auditory acuity ≥ grade 3 on CTCAE classification"}
• {"criterion_text":"- history of thermoregulation disorder"}
• {"criterion_text":"- impossibility of a rigorous medical follow-up due to geographic, social or mental reasons"}
• {"criterion_text":"- pregnant and lactating women"}
• {"criterion_text":"- significant intra-tumoral bleeding (hematoma) or ipsilateral subdural effusion"}
• {"criterion_text":"- contemporaneous treatment by anticoagulant or platelet aggregation inhibiting drugs"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- any contemporaneous treatment that, in the judgement of the clinical investigator, could induce brain toxicity after BBB disruption"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- radiotherapy during the last 6 weeks"}
• {"criterion_text":"- patient with another malignant tumour (other than the primary brain tumour) requiring concomitant treatment."}
• {"criterion_text":"- any other uncontrolled disease or active infection"}
• {"criterion_text":"- any other co-morbidity that could compromise participation to the study (in the judgement of the clinical investigator)"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- implanted defibrillator/pacemaker, neurostimulator, cochlear implant, intracerebral ferromagnetic vascular clip"}

Primary endpoints

• {"endpoint_text":"- Absence of Dose Limiting Toxicity (DLT) directly related to the ultrasound emission from the SonoCloud-9® device (3 emitters), assessed at each cycle","definition_or_measurement_approach":"DLT directly related to the ultrasound emission from the SonoCloud-9® device assessed at each treatment cycle (assessment at each cycle)."}

Secondary endpoints

• {"endpoint_text":"- Evaluation of the grade of blood-brain barrier (BBB) opening by ultrasound as described by Carpentier et al.","definition_or_measurement_approach":"Grading of BBB opening using the method described by Carpentier et al."}
• {"endpoint_text":"- overall survival (OS) at 3 months and progression-free survival (PFS) at 6 months","definition_or_measurement_approach":"Survival endpoints measured as OS at 3 months and PFS at 6 months."}
• {"endpoint_text":"- Evaluation of the occurrence of allergic and/or cardiac complications.","definition_or_measurement_approach":"Assessment and recording of allergic and cardiac complications."}
• {"endpoint_text":"- Evaluation of complications related to implantation or sonications (excluding ultrasound effects), evaluation of implantation and connection procedures, and assessment of the device's bioavailability and resistance.","definition_or_measurement_approach":"Monitoring and recording of implantation- and sonication-related complications, assessment of implantation/connection procedures and device bioavailability/resistance."}
• {"endpoint_text":"- Evaluation of clinical and/or radiological complications beyond the first treatment cycle.","definition_or_measurement_approach":"Clinical and radiological follow-up to identify complications after first cycle."}
• {"endpoint_text":"- Assessment of circulating tumor DNA, antigens or circulating tumor markers, and circulating tumor cells","definition_or_measurement_approach":"Measurement of circulating tumor DNA, tumor antigens/markers and circulating tumor cells (ancillary study)."}

France

Earliest CTIS Part Ii Submission Date

27-09-2024

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

572

Number Of Sites

3

Number Of Participants

24

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France