Safety of BBB Opening With the SonoCloud

NCT ID: NCT02253212

Last Updated: 2018-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2018-07-31

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.

Conditions

Glioblastoma; Glioma; Brain Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SonoCloud + carboplatin

SonoCloud : dose escalation Carboplatin : min 6 cycles - individual dose determination according to renal function and AUC

Group Type: EXPERIMENTAL

SonoCloud

Intervention Type: DEVICE

SonoCloud : dose escalation

Carboplatin

Intervention Type: DRUG

Carboplatin : min 6 cycles - individual dose determination according to renal function and AUC

Interventions

SonoCloud

SonoCloud : dose escalation

Intervention Type: DEVICE

Carboplatin

Carboplatin : min 6 cycles - individual dose determination according to renal function and AUC

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ahmed Idbaih, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Groupe Hospitalier Pitié Salpetriere - Neurosurgery Department

Paris, , France

Countries

France

References

Asquier N, Bouchoux G, Canney M, Martin C, Law-Ye B, Leclercq D, Chapelon JY, Lafon C, Idbaih A, Carpentier A. Blood-brain barrier disruption in humans using an implantable ultrasound device: quantification with MR images and correlation with local acoustic pressure. J Neurosurg. 2019 Feb 1;132(3):875-883. doi: 10.3171/2018.9.JNS182001. Print 2020 Mar 1.

Reference Type: DERIVED

PMID: 30717050 (View on PubMed)

Goldwirt L, Canney M, Horodyckid C, Poupon J, Mourah S, Vignot A, Chapelon JY, Carpentier A. Enhanced brain distribution of carboplatin in a primate model after blood-brain barrier disruption using an implantable ultrasound device. Cancer Chemother Pharmacol. 2016 Jan;77(1):211-6. doi: 10.1007/s00280-015-2930-5. Epub 2015 Dec 8.

Reference Type: DERIVED

PMID: 26645405 (View on PubMed)

Other Identifiers

2014-000393-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

P120905

Identifier Type: -

Identifier Source: org_study_id