Glioblastoma, Glioma, Brain Tumor
Conditions
Keywords
Blood brain barrier (BBB), Disruption, Low intensity pulsed ultrasound (LIPU), Sonocloud device, Glioblastoma (GBM), Brain Cancer, Carboplatin, Therapeutic Ultrasound
Brief summary
PURPOSE: The purpose of this study is to determine whether transient opening of the blood-brain barrier by pulsed ultrasound using the SonoCloud implantable ultrasound device is safely tolerated in patients with recurrent glioblastoma immediately before systemic delivery of carboplatin-based chemotherapy. STUDY HYPOTHESIS: The blood-brain barrier can be safely opened using pulsed ultrasound prior to chemotherapy administration in patients with recurrent glioblastoma. Transient opening of the blood-brain barrier by pulsed ultrasound will increase the glioblastoma exposure to carboplatin-based chemotherapy and increase progression-free and overall survival in patients with recurrent glioblastoma.
Detailed description
For patients with recurrent malignant gliomas, who have already been treated by a combination of surgery, radiation therapy and/or chemotherapy, few treatment options currently exist. Salvage therapies typically consist of systemic administration of chemotherapy agents, which have been shown to have limited effectiveness as median survival in this patient group is currently only 6 months. One limitation to the efficacy of systemic chemotherapy in the treatment of brain tumors is the blood-brain barrier (BBB). To enhance the delivery of systemically administered chemotherapy agents to brain tumors, an implantable ultrasound device was developed that can be used to temporarily disrupt the BBB. Delivery of pulsed ultrasound, in combination with an ultrasound contrast agent, has been shown to temporarily disrupt the BBB for a duration of more than 6 hours and allow for a significantly increased penetration of systemically administered chemotherapy drugs in pre-clinical studies. This study will evaluate the safety of temporary disruption of the BBB during carboplatin chemotherapy delivery in patients with recurrent glioblastoma. This study will also evaluate the maximum tolerated dose of ultrasound that can be used to disrupt the BBB. The use of dynamic contrast-enhanced MRI will be evaluated for determining the extent and magnitude of BBB opening. Clinical efficacy (Survival) and radiological efficacy (Progression Free Survival) will also be evaluated as secondary endpoints.
Interventions
DEVICESonoCloud
SonoCloud : dose escalation
DRUGCarboplatin
Carboplatin : min 6 cycles - individual dose determination according to renal function and AUC
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age greater than 18 years. * Subjects with recurrent glioma who have failed standard therapy with surgery and/or treatment with radiation and temozolomide. * Patient eligible for Carboplatin-based chemotherapy * Contrast-enhanced tumor less than 35 mm in diameter * No risk of cerebral herniation * Able to tolerate pre/post procedure steroid treatment * Social security affiliated (in France) * Able and willing to give signed and informed consent * Normal biological status * Hemoglobin ≥ 10 g/dl * Platelets ≥ 100000/mm3 * Neutrophils ≥ 1500/mm3 * Normal creatine clearance ≥ 60ml/mn * ASAT \< 3 N * ALAT \< 3 N * Normal Bilirubin Level \< 1.5 N * Alkaline Phosphatase \< 3 N * INR \< 1.5 * Prothrombin Level ≥ 70%
Exclusion criteria
* Allergic to Iodine, Gadolinium, Xylocain * Contra-indications to echographic contrast agent (microbubbles) * Severe Renal insufficiency * Hepatic insufficiency * Possible toxic treatment for CNS * Previously infected surgical field * Uncontrolled epilepsy * MRI contra-indications * Hemostasis troubles thrombopenia \<75.000, TP \<60%, INR \>1.5, anti-platelet or anticoagulant therapy on-going) * Active phlebitis or active pulmonary embolism * Pregnant or currently breast-feeding * Patients under judicial protection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety of transient disruption of the blood-brain barrier using the SonoCloud system in patients with recurrent glioblastoma. | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose of ultrasound with the SonoCloud system for transient disruption of the BBB. | 12 months |
| Quantification of the disruption of the BBB by the SonoCloud system using dynamic T1 contrast-enhanced MRI. | 12 months |
| Progression-free survival in patients treated with the SonoCloud system in combination with carboplatin chemotherapy. | 12 months |
| Overall survival in patients treated with the SonoCloud system in combination with carboplatin chemotherapy. | 12 months |
Countries
France
Outcome results
None listed