Multisite open-label randomized phase II clinical trial in newly diagnosed glioblastoma treated by concurrent TemoRadiation and adjuvant temozolomide +/- ultrasound-induced blood brain barrier opening - SonoFIRST

Prior treatment

• Patients with known intracranial aneurism, with and/or unremovable coils, clips, shunts, intravascular stents, wafer, non resorbable dura substitute, or reservoirs
• Patients with an uncontrolled intercurrent illness or any pre-existing comorbidities that in the Investigator’s opinion may prevent the implantation of the device or may impair the ability of the patient to receive treatment with SonoCloud or may be cofounding for evaluation of the clinical trial
• Patients with any following prohibited treatments: • Any investigational medicinal product within 30 days prior to inclusion and during the study • Antibiotics with known neurotoxicity (eg, aminoglycosides, cephalosporin, quinolones), unless substitution is not possible, • Non-absorbable material (dura matter substitute, hemostatic agent…) • Any other drug according investigator to cause cerebral toxicity due to BBB opening • Contra-indications to temozolomide
• Implantation of the SC-9 not possible according to neurosurgeon (Any patient morphological characteristics (e.g. skin thickness >9mm), which, from neurosurgeons’ opinion, prevent implantation of the device or may impair the ability of the patient to receive treatment with SonoCloud, would be excluded)
  • Contra indication Optune: If TTF treatment is initiated (only available in France), the investigator must first ensure that the patient has no contraindications to the Optune device (See page 41)

Other illness

• Patients with the following are not eligible: • Known arterial hypertension grade 3 or higher without adequate control on medications • Known or suspected unstable active or chronic infections requiring systemic treatment • Known significant cardiac disease: right-to-left shunts, Unstable angina pectoris, Symptomatic congestive heart failure, Unstable cardiac arrhythmia • Known significant pulmonary disease: severe pulmonary hypertension (pulmonary artery pressure > 90 mmHg), uncontrolled systemic hypertension, adult respiratory distress syndrome, or Pneumonitis • Known Severe renal failure • Known serious myelosuppression • Known Psychiatric illness/social situations that would limit compliance with study requirements • Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient’s safety or study endpoints • Known immunodeficiency disease or treatments (HIV) • Known viral or bacterial chronic/acute disease (potential blood borne infections that could result in meningitis or brain abscess) • Coeliac disease or wheat allergy • Known liver dysfunction
• Patients with uncontrolled epilepsy
• Patients with contra-indications to MRI or known sensitivity/allergy to gadolinium, or other intravascular contrast agents
• Known history of hypersensitivity reactions to perflutren lipid microsphere components or to any of the inactive ingredients in Luminity®/Definity®

Other

• Contra indication for sonication
• Patients under judicial protection
• Patients with multifocal tumor (unless all localized in a 70 mm diameter area accessible to ultrasound field) or located in posterior fossa tumor
• Patient with diffuse FLAIR abnormalities attributable to Gliomatosis
• Patients with evidence of uncontrolled intracranial pressure
• Patients with medical need to continue antiplatelet or antithrombotic treatment
• Pregnant or breastfeeding women (blood pregnancy test)

• Brain MRI with suspicion of newly diagnosed IDH wild type GBM
• Supratentorial tumor
• T1W Tumor enhancement of ≤ 7cm
• Eligible for partial or complete surgical resection and for concurrent TemoRadiation followed by adjuvant TMZ (according to Stupp protocol) with or without Tumor Treating Fields* - (*Tumor Treating Fields is applicable only in participating centers in France)
• Patient ≥ 18 years, able and willing to give signed and informed consent. Inclusion for patients aged >70 years should be validated in neuro-oncology tumor board (RCP)
• KPS ≥70