Safety and Efficacy of Transient Opening of the Blood-brain Barrier (BBB) With the SonoCloud-9

Conditions

Glioblastoma, Adult

Keywords

Recurrent Glioblastoma, Carboplatin, Ultrasound, Blood-brain barrier, Glioblastoma, SonoCloud, Low Intensity Pulsed Ultrasound (LIPU)

Brief summary

Recurrent glioblastoma (GBM) is a disease with high unmet clinical need. The standard of care for patients with GBM includes surgery, radiotherapy and chemotherapy. Despite this aggressive treatment, the overall median survival of patients with GBM remains at 15-20 months. In more than 95% of cases, tumor recurrence is observed within 2 cm to 3 cm of the resection cavity within 4-7 months after initial treatments. One of the main causes of recurrence is the inability of chemotherapies to enter the brain from the systemic circulation due to the blood-brain barrier (BBB). The BBB is unique to cerebral blood vessels and blocks most drugs from entering the brain in sufficient concentrations. The SonoCloud-9 (SC9) System delivers ultrasound to locally and transiently increase the permeability of the BBB to allow the passage of drugs into the cerebral parenchyma. The SC9 is dimensioned to cover the resection area and surrounding tissues in patients with recurrent GBM. The large sonicated volume covered by the SC9 device allows for broad BBB disruption and should allow for carboplatin chemotherapy to penetrate the surrounding tumor infiltrative area. By enhancing drug concentrations, it is hypothesized that further disease progression will be prevented.

Detailed description

This will be an open-label, Phase 1/2a, multicenter, single-arm, interventional trial that will first evaluate the dose limiting toxicity (DLT) of escalating numbers of ultrasound beams at constant acoustic pressure using a standard escalation (Phase 1) and then confirm the safety and efficacy of BBB opening (Phase 2a expansion).

Adam M. Sonabend, Rimas V. Lukas, Karan Dixit, Priya Kumthekar, Ditte Primdahl et al. (25 authors)

Neuro-Oncology2025-11-01

10.1093/neuonc/noaf201.0627

CTNI-37. SONOBIRD: A PHASE 3 TRIAL OF BLOOD-BRAIN-BARRIER (BBB) OPENING WITH THE SONOCLOUD-9 IN RECURRENT GLIOBLASTOMA PATIENTS RECEIVING IV CARBOPLATIN

Adam M. Sonabend, Olivier Chinot, Johnny Duerinck, Ángel Pérez‐Núñez, Dominique Higgins et al. (13 authors)

Neuro-Oncology2025-11-01

10.1093/neuonc/noaf201.0533

P17.07.A SONOBIRD: A PHASE 3 TRIAL OF BBB OPENING WITH THE SONOCLOUD-9 IN RECURRENT GLIOBLASTOMA PATIENTS RECEIVING IV CARBOPLATIN

Alexandre Carpentier, Johnny Duerinck, Ángel Pérez‐Núñez, Marjolein Geurts, Darlene Higgins et al. (12 authors)

Neuro-Oncology2025-10-01

10.1093/neuonc/noaf193.523

Abstract 3897: Isolation and molecular characterization of exosomes from glioblastoma patients using a microfluidic device after ultrasound-based opening of the blood-brain barrier

Abha Kumari, Mark W. Youngblood, Andrew Gould, Yoon‐Tae Kang, Li Chen et al. (14 authors)

Cancer Research2024-03-222 citations

10.1158/1538-7445.am2024-3897

389 Combination Therapy With Paclitaxel, Carboplatin, and Low-Intensity Ultrasound for Recurrent Glioblastoma: Rationale for Ongoing Phase II Clinical Trial

Karl J. Habashy, Crismita Dmello, Li Chen, Víctor A. Arrieta, Kwang‐Soo Kim et al. (9 authors)

Neurosurgery2024-03-15

10.1227/neu.0000000000002809_389

Repeated blood-brain barrier opening with a nine-emitter implantable ultrasound device in combination with carboplatin in recurrent glioblastoma: a phase I/II clinical trial.

Carpentier A, Stupp R, Sonabend AM, Dufour H, Chinot O, Mathon B, Ducray F, Guyotat J, Baize N, Menei P, de Groot J, Weinberg JS, Liu BP, Guemas E, Desseaux C, Schmitt C, Bouchoux G, Canney M, Idbaih A.

2024-02-2366 citations

10.1038/s41467-024-45818-7

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Neuro-Oncology2023-11-01

10.1093/neuonc/noad179.0417

Repeated blood-brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in patients with recurrent glioblastoma: a phase 1 trial.

Sonabend AM, Gould A, Amidei C, Ward R, Schmidt KA, Zhang DY, Gomez C, Bebawy JF, Liu BP, Bouchoux G, Desseaux C, Helenowski IB, Lukas RV, Dixit K, Kumthekar P, Arrieta VA, Lesniak MS, Carpentier A, Zhang H, Muzzio M, Canney M, Stupp R.

2023-05-01144 citations

10.1016/s1470-2045(23)00112-2

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Alexandre Carpentier, Adam M. Sonabend, Roger Stupp, Olivier Chinot, Henry Dufour et al. (12 authors)

Neuro-Oncology2022-11-011 citations

10.1093/neuonc/noac209.286

OS07.3.A Phase 1/2 clinical trial of blood-brain barrier opening with the SonoCloud-9 implantable ultrasound device in recurrent glioblastoma patients receiving IV carboplatin

Ahmed Idbaïh, Adam M. Sonabend, R Stupp, Olivier Chinot, Henry Dufour et al. (10 authors)

Neuro-Oncology2022-09-011 citations

10.1093/neuonc/noac174.048

A phase I/IIa study to evaluate the safety and efficacy of blood-brain barrier (BBB) opening with the SonoCloud-9 implantable ultrasound device in recurrent glioblastoma patients receiving IV carboplatin.

Ahmed Idbaïh, François Ducray, Roger Stupp, Nathalie Baize, Olivier Chinot et al. (15 authors)

Journal of Clinical Oncology2021-05-2013 citations

10.1200/jco.2021.39.15_suppl.2049

CTNI-31. INTERIM RESULTS OF A PHASE I/IIA STUDY TO EVALUATE THE SAFETY AND EFFICACY OF BBB OPENING WITH THE SONOCLOUD-9 IMPLANTABLE ULTRASOUND DEVICE IN RECURRENT GLIOBLASTOMA PATIENTS PRIOR TO IV CARBOPLATIN

Ahmed Idbaïh, François Ducray, Roger Stupp, Nathalie Baize, Olivier Chinot et al. (15 authors)

Neuro-Oncology2020-11-011 citations

10.1093/neuonc/noaa215.198

ACTR-57. A PHASE 1/2 STUDY TO EVALUATE THE SAFETY AND EFFICACY OF BLOOD-BRAIN BARRIER (BBB) OPENING WITH A NINE-EMITTER IMPLANTABLE ULTRASOUND DEVICE IN RECURRENT GLIOBLASTOMA PATIENTS PRIOR TO CARBOPLATIN

Ahmed Idbaïh, François Ducray, John DeGroot, Roger Stupp, Jacques Guyotat et al. (12 authors)

Neuro-Oncology2019-11-01

10.1093/neuonc/noz175.099

P05.05 Safety and feasibility of temporary blood-brain barrier disruption with the SonoCloud-1/3 implantable ultrasound device in recurrent glioblastoma

Ahmed Idbaïh, Michael Canney, Guillaume Bouchoux, Carole Desseaux, Alexandre Vignot et al. (10 authors)

Neuro-Oncology2019-08-012 citations

10.1093/neuonc/noz126.119

Interventions

DEVICESonoCloud-9

Escalating numbers of ultrasound beams at constant acoustic pressure

DRUGCarboplatin

Dose of carboplatin infusion is AUC4-6

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

Key Inclusion Criteria: 1. Age ≥ 18 years, able and willing to give signed and informed consent. 2. Patient with histologically proven recurrent de novo GBM: 1. After at least a first-line standard of care (maximal safe resection, if feasible, radiation with temozolomide \[TMZ\], then TMZ); 2. Any recurrence; 3. Bevacizumab-naïve.\* 3. Patient eligible for carboplatin-based chemotherapy. 4. Patient eligible for a surgical resection. 5. Maximal tumor diameter at inclusion (pre surgery) ≤ 70 mm in T1wMRI. 6. Patients should be stable, without evidence of a midline shift, significant peritumoral edema, or rapid progression of clinical symptoms. 7. Karnofsky performance status ≥ 70. 8. Patient receiving prednisone dose ≤ 40 mg (dexamethasone ≤ 6 mg) for at least 7 days. Key

Exclusion criteria

1. Multifocal tumor (unless all localized in a 70 mm diameter area). 2. Patients at risk of surgery site infection (2 or more previous craniotomies, neurosurgery within the last 3 months, poor skin condition, and/or previously infected surgical field). 3. Posterior fossa tumor. 4. Uncontrolled epilepsy. 5. Patients with evidence of uncontrolled intracranial pressure. 6. Patients with known intracranial aneurism or having presented intra-tumor spontaneous hemorrhage. 7. Patients with coils, clips, shunts, intravascular stents, and/or unremovable wafer, non resorbable dura substitute, or reservoirs. 8. Patients with medical need to continue antiplatelet therapy. 9. Patients with known or suspected active or chronic infections.

Design outcomes

Primary

Measure	Time frame	Description
Dose limiting toxicity (DLT) of number of activated ultrasound beams	15 days after the first sonication treatment	DLT will be evaluated using imaging (MRI) and clinical examination, as CTCAE that occurs within 2 weeks of the first sonication and that does not respond to optimal medical management (including steroids) within 7 days.
Blood-Brain Barrier (BBB) opening	At the end of the first three sonication treatments (treatment occurs every 4 weeks)	BBB opening will be evaluated by contrast-enhanced T1w magnetic resonance imaging (MRI)

Countries

France, United States

Outcome results

None listed