Safety of BBB Opening With the SonoCloud

Phase 1

Completed

• Conditions: Glioma; Brain Tumor; Glioblastoma
• Interventions: Device: SonoCloud; Drug: Carboplatin

• Registration Number: NCT02253212
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Study Timeline

• Study Start: 2014-07
• Study First Submitted: 2014-09-29
• Study First Submitted QC: 2014-09-29
• Study First Posted: 2014-10-01
• Primary Completion: 2018-07
• Study Completion: 2018-07
• Status Verified: 2018-10
• Last Update Submitted: 2018-10-10
• Last Update Posted: 2018-10-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SonoCloud + carboplatin	Carboplatin	SonoCloud : dose escalation Carboplatin : min 6 cycles - individual dose determination according to renal function and AUC
SonoCloud + carboplatin	SonoCloud	SonoCloud : dose escalation Carboplatin : min 6 cycles - individual dose determination according to renal function and AUC

Primary Outcome Measures

Name	Time	Method
Safety of transient disruption of the blood-brain barrier using the SonoCloud system in patients with recurrent glioblastoma.	12 months

Secondary Outcome Measures

Name	Time	Method
Maximum tolerated dose of ultrasound with the SonoCloud system for transient disruption of the BBB.	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
Quantification of the disruption of the BBB by the SonoCloud system using dynamic T1 contrast-enhanced MRI.	12 months

Trial Locations

Locations (1)

Groupe Hospitalier Pitié Salpetriere - Neurosurgery Department; 🇫🇷 Paris, France