Sonocloud-9 in Association With Carboplatin Versus Standard-of-Care Chemotherapies (CCNU or TMZ) in Recurrent GBM

Eligibility Criteria

• 1. Histologically proven glioblastoma (WHO criteria 2021), absence of IDH mutation demonstrated by negative IDH1 R132H staining on Immunohistochemistry.
• 2. Patient must have received prior first line therapy that must have contained both:
• 1. Prior surgery or biopsy and standard fractionated radiotherapy (1.8-2 Gy/fraction, \>56 Gy\<66 Gy) or hypofractionated radiotherapy (15 x 2.66 Gy or similar regimen)
• 2. One line of maintenance chemotherapy and/or immune- or biological therapy, (with or without Tumor-Treating Fields)
• 3. First, unequivocal disease progression with
• 1. measurable tumor (\>100 mm2 or 1 cm3, based on RANO criteria) documented (e.g., increase of 25% in tumor diameter) on MRI performed within 14 days of inclusion and,
• 2. interval of a minimum of 12 weeks since the completion of prior radiotherapy, unless there is a new lesion outside the radiation field or unequivocal evidence of viable tumor on histopathological sampling
• 4. Patient is candidate for craniotomy and at least 50% resection of enhancing region
• 5. Maximal enhancing tumor diameter prior to inclusion ≤ 5 cm on T1w. (In case of planned lobectomy, post operative peritumoral brain or residual size ≤5 cm)
• 6. WHO performance status ≤ 2 (equivalent to Karnofsky Performance Status (KPS) ≥ 70)
• 7. Age ≥ 18 years
• 8. Participant must be recovered from acute toxic effects (\<grade 2) of all prior anticancer therapy. Interval since last therapy to presumed date of surgery of at least:
• 1. ≥ 4 weeks or 5 half-lives (whichever is shorter) for
• * Cytotoxic
• * Other small chemical entity (e.g., targeted therapy)
• * For biologics (e.g., antibodies, except bevacizumab)
• 2. ≥ 6 weeks of prior bevacizumab
• 9. Adequate hematologic, hepatic, and renal laboratory values within 14 days of inclusion i.e.:
• 1. Hemoglobin ≥ 10 g/dL, platelets ≥ 100,000/mm3, neutrophils ≥ 1500/mm3.
• 2. Liver function test with ≤ grade 1 alterations, except if due to antiepileptic drug therapy or isolated increased bilirubin due to Gilbert syndrome
• 3. Estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2 using Cockcroft Gault formula
• 10. Patient able to understand clinical trial information and willing to provide signed and informed consent
• 11. Patient of childbearing potential must have a negative pregnancy test within 14 days of inclusion and must agree to use a medically-acceptable method of birth control during the treatment period and, if randomized in the experimental arm, for at least 1 month after the last cycle of carboplatin
• 12. A male patient must agree to use condoms during the treatment period and, if randomized in the experimental arm, for at least 3 months after the last cycle of carboplatin; the patient must also refrain from donating sperm during this period.
• 13. Patient must be a beneficiary of a health plan that covers routine patient care costs. Patient must be a beneficiary of or affiliated with a social security scheme (according to country-specific requirements)