Innovative SonoCloud-9 Device for Blood Brain Barrier Opening in First Line Temozolomide Glioblastoma Patients.
- Conditions
- Eligible for the Standard of Care Including Concurrent Temoradiation and Adjuvant TemozolomideInitial Radiological Diagnosis Compatible With Newly Diagnosed Glioblastoma (IDH Wild-type)Initial Radiological Diagnosis Eligible for Tumor Resection
- Interventions
- Device: SonoCloud-9 (SC9) device
- Registration Number
- NCT04614493
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
Glioblastoma (GBM) is an aggressive cancer with a progression-free survival (PFS) of 7 months and an overall survival (OS) of 15 months. Many therapeutic approaches have failed to improve the prognosis of patients to date. One of the main reasons is the presence of blood brain barrier (BBB) which limits therapeutic agents uptake in the brain. GBM is also considered to have a "cold" (unresponsive) immunological microenvironment due to factors released by the tumor and the presence of BBB limiting the transit of immune cells from the systemic circulation. Therefore, by-passing the BBB appears as a promising strategy.
The objective of the Phase II clinical trial, SonoFIRST, is to evaluate if the use of therapeutic ultrasound device, sonoCloud-9 (SC9) could improve the progression free survival of newly diagnosed GBM patients, treated by concurrent temoradiation and adjuvant temozolomide. The transient opening of the BBB by ultrasound with the SonoCloud-9 (SC9) device, predicts the increase in the penetration of temozolomide (TMZ) into the brain and the stimulation of cerebral immunity with the prospect of improving the survival of 160,000 new brain tumor patients each year in Europe and the United States.
- Detailed Description
This will be an open-label, Phase 2, multicenter, double arm, randomized, interventional trial that will evaluate primarily the clinical efficacy of the device and will be to compare Progression Free Survival (PFS) between the standard of care treatment with concomitant ultrasound BBB opening versus standard of care alone. Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Currently, prognosis is very poor, with a survival of about 15 months with current therapies. Although intensive treatments combining surgery, radiotherapy and chemotherapy, the prognosis of GBM patients remains poor. New treatment strategies are urgently needed.
In the brain, the presence of the blood-brain barrier (BBB) limits the uptake of therapeutic agents. To encounter this BBB issue, Professor Alexandre Carpentier and his team developed an ultrasound medical device (SonoCloud), implanted in the skull during surgery. This highly innovative technique temporarily permeates the BBB, increasing drug delivery to the brain by five times. The SonoCloud, a low-intensity pulsed ultrasound device developed by CarThera, is one of the major innovations in this field, as shown by the encouraging results obtained in studies in recurrent GBM.
The expected benefits of using the SonoCloud-9 experimental device prior to TMZ chemotherapy are the stabilization or reduction of GBM tumor volume on the one hand, and stabilization or improvement of the patient's neurological status on the other hand.
Participation in the clinical trial will contribute to a better understanding of the safety and efficacy of opening the BBB. It will be possible to determine whether the BBB opening using low-intensity pulsed ultrasound can be effective in treating GBM, in addition to the standard of care protocol.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 66
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ultrasound experimental arm Temozolomide according Stupp protocol Standard of Care + 15 Ultrasound BBB opening Ultrasound experimental arm SonoCloud-9 (SC9) device Standard of Care + 15 Ultrasound BBB opening Control arm Temozolomide according Stupp protocol Standard of Care
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS), 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 criteria) or death due to any cause. Between randomisation and 18 months after the last inclusion. Progression will be assessed by local investigator according to the RANO criteria
- Secondary Outcome Measures
Name Time Method immune Progression Free Survival (iPFS) Between randomisation and 18 months after the last inclusion. The iPFS is evaluated according to iRANO (immune-related modifications / pseudo-progression ) criteria assessed by local investigator
Esthetical Before surgery, pre-TemoRadiation visit, Cycle1 (baseline after surgery/radiotherapy, 1 cycle = 28 days), Cycle 3, Cycle 6, Month 11, Month 18, or until progression up to 18 months score in self-confidence concerning esthetical dimension of surgical scar using esthetical comfort question equivalent to q39 of QLQ-BR23 questionnaire: Does your skull scar induce any esthetic burden to you?
1. Not at all
2. A little
3. Quite a bit
4. Very muchcentral review Progression Free Survival (crPFS) Between randomisation and 18 months after the last inclusion. The central review Progression Free Survival is evaluated by a central assessment (independent imaging core lab) at the end of study and is defined as the time between randomization and tumor progression which is the first documented tumor progression according to the radiological RANO criteria or death due to any cause
Mean score of Patient quality of life preservation - EORTC Quality of Life Questionnaire C30 Before surgery, pre-TemoRadiation visit, Cycle 1 (baseline after surgery/radiotherapy, 1 cycle = 28 days), Cycle 3, Cycle 6, Month 11 and Month 18, or until progression up to 18 months Quality of Life Questionnaire (QLQ) according to the European Organization for Research and Treatment of Cancer will be assessed by mean scores of the EORTC QLQ C-30 questionnaire (30 questions, score from 30 to 126) by local investigator or nurses and patient
Visual analogic scale (VAS) Pain score from surgical area Before surgery, pre-TemoRadiation visit, Cycle1 (baseline after surgery/radiotherapy, 1 cycle = 28 days), Cycle 3, Cycle 6, Month 11, Month 18, or until progression up to 18 months pain score from surgical area using visual analogic scale (score 0 to 10. Zero indicates the absence of pain, while 10 represents the most intense pain possible).
Safety : Type, frequency and severity of adverse events and serious adverse events From inclusion to end of treatment, up to 18 months Safety confirmation of efficient blood brain barrier opening procedure with the SonoCloud-9 system. Safety confirmation is assessed by the frequency and severity of Adverse Events (AE) (incidence of AE summarized by system organ class and/or preferred term and severity) based on the Common Terminology Criteria for Adverse Events, version 5.0.
Mean score Patient quality of life preservation - BN20 Quality of Life Questionnaire Before surgery, pre-TemoRadiation visit, Cycle1 (baseline after surgery/radiotherapy, 1 cycle = 28 days), Cycle 3, Cycle 6, Month 11, Month 18, or until progression up to 18 months Quality of Life Questionnaire (QLQ) according to the European Organization for Research and Treatment of Cancer will be assessed will be assessed by means of the EORTC BN20 questionnaire (30 questions, score from 1 to 80) by local investigator or nurses and patient
Karnofsky Performance Status (KPS) Before surgery, Surgery (+/- device implantation), pre-TemoRadiation visit, start and day 15 of each cycle (=28 days) from Cycle 1 to 6, Month 11, Month 13, Month 15, or until progression up to 18 months, new surgery (debulking or device explantation) Mean score of Patient cognitive preservation Before surgery, pre-TemoRadiation visit, Cycle1 (baseline after surgery/radiotherapy, 1 cycle = 28 days), Cycle 3, Cycle 6, Month 11, Month 18, or until progression up to 18 months Mini Mental Status Examination (30-point questionnaire, score from 1 to 30) mean score assessed by local investigator or nurses and patient
Overall Survival improvement (OS) Between randomisation and 18 months after the last inclusion. OS is defined as the time from the date of randomization to the date of death due to any cause.
Trial Locations
- Locations (7)
Katholieke Universiteit Leuven
🇧🇪Leuven, Belgium
Centre hospitalier Universitaire d'Angers
🇫🇷Angers, France
Groupe Hospitalier Saint-André
🇫🇷Bordeaux, France
AP-HM, La Timone, Hôpital Universitaire
🇫🇷Marseille, France
Hospices Civils de Lyon, Hôpital Pierre Wertheimer
🇫🇷Bron, France
APHP-Sorbonne, Pitié Salpêtrière Hospital
🇫🇷Paris, France
Centre hospitalier universitaire vaudois CHUV
🇨🇭Lausanne, Switzerland