AI-Powered Research

1. Histologically proven glioblastoma (WHO criteria 2021), absence of IDH
mutation demonstrated by negative IDH1 R132H staining on IHC. 2. Patient must
have received prior first line therapy that must have contained both: a) 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) b) One line of maintenance chemotherapy and/or immune- or biological
therapy, (with or without TTFields) 3. First, unequivocal disease progression
with a) 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, b) 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
(

Exclusion Criteria

1. Multifocal enhancing tumor on T1w (unless all localized in a 5 cm diameter
area)
2. Posterior fossa tumor
3. Known BRAF/ NTKR mutated patients
4. Patient at risk of surgery site infection (e.g., 2 or more previous
craniotomies/neurosurgery within the last 3 months, poor skin condition, and/or
previously infected surgical field, or any other condition that is of increased
infectious risk in the opinion of the neurosurgeon)
5. Patient treated at high, stable -or average- dose of corticosteroids (>= 6
mg/day dexamethasone or equivalent) in the 7 days prior to inclusion. Patients
on dexamethasone for reasons other than mass effect may still be enrolled.
6. Contra-indication to carboplatin, CCNU or TMZ
7. Known history of hypersensitivity reactions to perflutren lipid microsphere
components or to any of the inactive ingredients in ultrasound resonator
8. Patient has received bevacizumab for other reasons (such as tumor
progression) than treating edema
9. Peripheral neuropathy or neuropathy >= grade 2
10. Uncontrolled epilepsy or evidence of intracranial pressure
11. Patient with known intracranial aneurism or having presented intra-tumor
significant spontaneous hemorrhage
12. Patient with unremovable coils, clips, shunts, intravascular stents, and/or
wafer, or reservoirs
13. Patient with medical need to be on continued anti-platelet aggregation
therapy and/or anticoagulation. Patients for whom anticoagulation/platelet
aggregation can be temporarily interrupted may be eligible after discussion and
prior authorization by the sponsor.
14. Patient receiving enzyme-inducing antiepileptic drugs (namely phenytoin,
carbamazepine and derivatives, phenobarbital), unless switched on another
antiepileptic regimen
15. History of other malignancy within 3 years prior to study start with the
exception of adequately treated basal cell carcinoma, squamous cell carcinoma,
non-melanomatous skin cancer or carcinoma in situ of the uterine cervix
16. Patient with known or suspected active or chronic infections
17. Patient with known significant cardiac disease, known to have right-to-left
shunts, severe pulmonary hypertension (pulmonary artery pressure > 90 mm Hg),
uncontrolled systemic hypertension, or acute respiratory distress syndrome
18. Known sensitivity/allergy to gadolinium, or other intravascular contrast
agents
19. Patient with impaired thermo-regulation or temperature sensation
20. Pregnant, or breastfeeding patient
21. Any other serious patient medical or psychological condition that may
interfere with adequate and safe delivery of treatment and care (e.g., positive
human immunodeficiency virus [HIV] status, potential blood-borne infections,*),
circumstance (e.g., sinus opening during surgery), psychological, morphological
characteristics (e.g., skin characteristics, bone thickness), or any
pre-existing comorbidities that in the investigator*s opinion may prevent the
implantation of the device, may impair the ability of the patient to receive
treatment with SonoCloud-9 or may be confounding for evaluation of the clinical
trial endpoints
22. Patients under guardianship, curatorship, under legal protection or
deprived of liberty by an administrative or judicial decision

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Overall survival (OS), defined as the time from the date of randomization to<br /><br>the date of death due to any cause or censored at the time of last follow-up,<br /><br>calculated according to the Kaplan Meier method.</p><br>

Secondary Outcome Measures