Newly diagnosed Glioblastoma (IDH wild-type) patients at initial radiological diagnosis eligible for tumor resection and for the standard of care including concurrent temoradiation and adjuvant TMZ. The SonoCloud-9 ultrasound System is intended to locally and transiently increase the permeability of the blood brain barrier to Increase temozolomide (TMZ) brain uptake and endogenous brain immunity.
Conditions
Interventions
Trade Name: TEMOZOLOMIDE 5mg
Product Name: TEMOZOLOMIDE
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: temozolomide
Other descriptive name: TEMOZOLOMIDE
Concentration unit: mg milligram(s)
Co
Sponsors
Assistance Publique Hopitaux de Paris
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria 1. Age = 18 years and = 70 years, able and willing to give signed and informed consent 2. MRI with suspicion of GBM or Patient with a newly histologically proven IDHwt GBM by previous stereotaxic biopsy or king size opened biopsy 3. Karnofsky Performance Status = 70 4. Patient eligible for a total or sub-total surgical tumor resection 5. Maximal tumor enhancement diameter at inclusion (pre surgery) = 70 mm in T1W MRI 6. Patient eligible after surgery for the first line standard of care temoradiation and adjuvant TMZ (Stupp protocol, 54) 7. Patient with adequate organ and bone marrow function within 14 days prior to registration, as defined below: - Hemoglobin = 10.0 g/dL - Leukocytes = 3,000/L - Absolute neutrophil count = 1,500/L - Platelets = 100,000/L - Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 33
Exclusion criteria
Exclusion criteria: 1. Patients with multifocal tumor (unless all localized in a 70 mm diameter area accessible to ultrasound field) or located in posterior fossa tumor 2. Patient with diffuse FLAIR abnormalities attributable to Gliomatosis 3. Patients with evidence of uncontrolled intracranial pressure 4. Patients with uncontrolled epilepsy 5. Patients with medical need to continue antiplatelet or antithrombotic treatment 6. Pregnant or breastfeeding women (blood pregnancy test) 7. Patients with contra-indications to MRI or known sensitivity/allergy to gadolinium, or other intravascular contrast agents 8. Known history of hypersensitivity reactions to perflutren lipid microsphere components or to any of the inactive ingredients in Luminity®/Definity® 9. Patients with known intracranial aneurism, with and/or unremovable coils, clips, shunts, intravascular stents, wafer, non resorbable dura substitute, or reservoirs 10. 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. 11. 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) 12. Patients under judicial protection 13. 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 - Dacarbazine hypersensitivity 14. Implantation of the SC-9 not possible according to neurosurgeon (any patient morphological characteristics (e.g. skin thin 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: clinical efficacy based on comparison of median PFS (Progression Free Survival) assessed by local investigator between the standard of care treatment with ultrasound BBB opening versus standard of care treatment alone.;Secondary Objective: -Survival improvement, -Patient quality of life preservation, -Patient intellectual preservation, -Safety confirmation of SonoCloud-9 induced efficient grade 3 BBB opening.;Primary end point(s): Progression Free Survival (PFS) is defined as the time between randomization and disease progression which is the first documented tumor progression (per local Investigator assessment according to the RANO) or death due to any cause. PFS rate at 6, 12, 18 and 24 months and median-PFS will be described. The “baseline MRI” is performed 1 month after radiotherapy completion. The disease progression is judge on the subsequent MRI performed every 2 months, with comparison to the “baseline MRI”. ;Timepoint(s) of evaluation of this end point: LSLV | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - crPFS: central review Progression Free Survival according to RANO criteria assessed by central review - iPFS: immune Progression Free Survival according to iRANO criteria assessed by local investigator - OS : Overall Survival - KPS: Karnofsky Performance Status assessed at all visits until progression by assessed by local investigator or nurses. - MMSE: Mini Mental Status Examination mean score assessed at randomization, pre-TemoRadiation visit, C1 (baseline after surgery/radiotherapy), C3, C6, M11 and M18 until progression by local investigator or nurses and patient. - QLQ-C30: The C30 Quality of Life Questionnaire (QLQ) according to the European Organization for Research and Treatment of Cancer will be assessed at randomization, pre-TemoRadiation visit, C1 (baseline after surgery/radiotherapy), C3, C6, M11 and M18 until progression by local investigator or nurses and patient. - QLQ-BN20PROM: The BN20 Quality of Life Questionnaire (QLQ) according to the European Organization for Research and Treatment of Cancer will be assessed at randomization, pre-TemoRadiation visit, C1 (baseline after surgery/radiotherapy), C3, C6, M11 and M18 until progression by local investigator or nurses and patient. - PainPROM: Pain score from surgical area according to visual analogic scale will be assessed at randomization, pre-TemoRadiation visit, C1 (baseline after surgery/radiotherapy), C3, C6, M11 and M18 until progression, by local investigator or nurses and patient - EstheticalPROM: score in self-confidence concerning esthetical dimension of surgical scar will be assessed at randomization, pre-TemoRadiation visit, C1 (baseline after surgery/radiotherapy), C3, C6, M11 and M18 until progression according to esthetical comfort question equivalent to q39 of QLQ-BR23 questionnaire by local investigator or nurses and patient: Does your skull scar induce any esthetic burden to you? 1-Not at all 2-A little 3-Quite a bit 4-Very much - Safety confirmatio | — |
Countries
Belgium, France, Switzerland
Contacts
Public ContactDRCI Hôpital St Louis
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Outcome results
None listed