Safety of BBB Opening With the SonoCloud (SONOCLOUD)

Assistance Publique - Hôpitaux de Paris

Status and phase

Completed

Phase 2

Phase 1

Conditions

Glioblastoma

Glioma

Brain Tumor

Treatments

Device: SonoCloud

Drug: Carboplatin

Study type

Interventional

Funder types

Other

Identifiers

NCT02253212

P120905

2014-000393-19 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment

27 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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