Safety Study of the Repeated Opening of the Blood-brain Barrier With the SonoCloud® Device to Treat Malignant Brain Tumors in Pediatric Patients

Launched by ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS · Mar 14, 2022

Keywords

ClinConnect Summary

This clinical trial is exploring a new way to treat certain types of malignant brain tumors in children using a device called SonoCloud-9. The goal is to safely open the blood-brain barrier—a protective layer around the brain—using ultrasound before giving chemotherapy (a cancer treatment) with a drug called carboplatin. By temporarily opening this barrier, the treatment aims to allow the chemotherapy to reach the tumor more effectively, potentially improving outcomes for young patients with recurrent brain tumors.

To participate in the study, children aged 5 to 17 years old who have a specific type of brain tumor that has come back after previous treatments may be eligible. They should be able to undergo ultrasound and MRI scans without needing sedation. Participants will receive treatment and monitoring to ensure their safety throughout the trial. This study is currently recruiting participants, and their health insurance must cover the costs associated with the trial. It's important for families to discuss this opportunity with their healthcare provider to see if it's a good fit for their child.

Gender

ALL

Eligibility 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