Eligibility criteria

Target population:

Adults with newly diagnosed glioblastoma, non-mutated IDH, at the time of initial radiological diagnosis and eligible for tumour resection and the currents standards of cares: the Stupp protocol, i.e. concomitant Temozolomide and adjuvant consolidation phase alone.

Inclusion criteria :

1. Age ≥ 18 years and ≤ 70 years, able to give free and informed consent.
2. Brain MRI with suspicion of newly diagnosed GBM non-mutated IDH.
3. Karnofsky index ≥ 70
4. Patient eligible for total or partial surgical resection of the tumour
5. Tumour extension at inclusion ≤ 7cm (T1W)
6. Patients eligible for partial or complete surgical resection and TemoRadiation followed by adjuvant TMZ (according to the current Stupp standard of care protocol)
7. Patients with adequate organ and bone marrow function within 14 days prior to inclusion, as defined below:
   • Hemoglobin ≥ 10.0 g/dL
   • Leukocytes ≥ 3,000/L
   • Neutrophils ≥ 1,500/L
   • Platelets ≥ 100,000/L
   • Total bilirubin < 1.5 x LSN
   • AST(SGOT)/ALT(SPGT) ≤ 3 x LSN
   • Alkaline phosphatase (PAL) < 3 x LSN
   • Normal creatinine clearance≥ 60 ml/minute.
   • Prothrombin time and partial thromboplastin time within institutional limits.
8. For women of childbearing potential, a negative pregnancy test prior to enrolment and an acceptable method of medication contraception used throughout the study are required. A patient may participate in the study if she is not pregnant or breastfeeding and at least one of the following conditions applies: Not a woman of childbearing potential OR a woman of childbearing potential who agrees to follow contraceptive advice during the treatment period and for at least one month after the end of study visits
9. Sexually active men with a woman of childbearing potential who agree to follow instructions for contraceptive method(s) during the treatment period and for 6 months after the last TMZ cycle. They should refrain from donating sperm during this period.
10. Written, dated and signed informed consent prior to any specific research procedure (collection, processing and testing).
11. Affiliation to a French social security system (beneficiary or beneficiary’s family) excluding the AME.

Non-inclusion criteria:

1. Patients with multifocal tumours (unless all are located within a 70 mm diameter area accessible to the ultrasound field) or located in the posterior tumour fossa
2. Patients with diffuse FLAIR abnormalities due to gliomatosis,
3. Patients with evidence of uncontrolled intracranial pressure,
4. Patients with uncontrolled epilepsy,
5. Patients requiring continued anti-platelet or anti-thrombotic therapy,
6. Pregnant women (blood pregnancy test) or nursing mothers
7. Patients with contraindications to MRI or known sensitivity/allergy to gadolinium or other intravascular contrast agents,
8. Patients with a known history of hypersensitivity reactions to the components of the perflutrene lipid microspheres or to any of the inactive ingredients of Luminity®/Definity®.
9. Patients with known intracranial aneurysms, with and/or without coils, clips, shunts, intravascular stents, wafer, non-absorbable dura mater substitutes or reservoirs,
10. Patients with uncontrolled intercurrent disease or any pre-existing comorbidity that, in the opinion of the investigator, may preclude implantation of the device or may interfere with the patient’s ability to receive treatment with the SonoCloud or may be created for the evaluation of the clinical trial,
    • Known grade 3 or higher hypertension,
    • Known or suspected infections or unstable chronic infections requiring systemic treatment,
    • Known significant heart disease: right-left shunts, unstable angina, symptomatic congestive failure, unstable arrhythmia,
    • Known significant pulmonary disease: severe pulmonary hypertension (pulmonary arterial pressure > 90 mmHg), adult respiratory distress syndrome or pneumonia
    • Known severe renal impairment,
    • Known severe myelosuppression,
    • Known psychiatric illnesses/social situations that would limit compliance with study requirements,
    • Any other illness or condition that, in the opinion of the local investigator, would interfere with study compliance or compromise patient safety or study outcomes,
    • Known immunodeficiency (HIV) disease or treatment,
    • Known chronic/active viral or bacterial diseases (potential bloodstream infections that could lead to meningitis or brain abscess),
11. Patients under judicial protection,
    • Patients who are undergoing prohibited treatment such as:Any investigational drug within 30 days prior to inclusion and during the study,
    • Antibiotics of known neurotoxicity (e.g. aminoglycosides, cephalosporin, quinolones), unless substitution is not possible,
    • Non-absorbable material (dura mater substitute, haemostatic agent…)
    • Any other drug that, in the opinion of the investigator, would cause brain toxicity due to BBB opening,
    • Contraindications to temozolomide use,
    • Implantation of the SC-9 not possible in the opinion of the neurosurgeon (any morphological features of the patient that, in the opinion of the neurosurgeons, preclude implantation of the device or may interfere with the patient’s ability to receive treatment with the SonoCloud would be excluded)