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

NCT03744026 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: SC9-GBM-01
• Study Type: interventional
• Target: 38
• Locations: 2 countries
• Sites: 6

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.

Conditions

Glioblastoma, Adult

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (DLT) of number of activated ultrasound beams

  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.

  15 days after the first sonication treatment

• Blood-Brain Barrier (BBB) opening

  BBB opening will be evaluated by contrast-enhanced T1w magnetic resonance imaging (MRI)

  At the end of the first three sonication treatments (treatment occurs every 4 weeks)

Study Arms (1)

SonoCloud-9 Ultrasound + Carboplatin

EXPERIMENTAL

SonoCloud-9 Carboplatin: 6 cycles (every 4 weeks)

Device: SonoCloud-9; Drug: Carboplatin

Interventions

SonoCloud-9 DEVICE

Escalating numbers of ultrasound beams at constant acoustic pressure

SonoCloud-9 Ultrasound + Carboplatin

Carboplatin DRUG

Dose of carboplatin infusion is AUC4-6

SonoCloud-9 Ultrasound + Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Multifocal tumor (unless all localized in a 70 mm diameter area).
• 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).
• Posterior fossa tumor.
• Uncontrolled epilepsy.
• Patients with evidence of uncontrolled intracranial pressure.
• Patients with known intracranial aneurism or having presented intra-tumor spontaneous hemorrhage.
• Patients with coils, clips, shunts, intravascular stents, and/or unremovable wafer, non resorbable dura substitute, or reservoirs.
• Patients with medical need to continue antiplatelet therapy.
• Patients with known or suspected active or chronic infections.

Sponsors & Collaborators

• CarThera: lead

Study Sites (6)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

CHU

Angers, France

Location

Hôpital Neurologique Pierre Wertheimer

Bron, France

Location

Hôpital de La Timone

Marseille, France

Location

Hôpital de la Pitié-Salpêtrière

Paris, France

Location

Related Publications (2)

• Carpentier A, Canney M, Vignot A, Reina V, Beccaria K, Horodyckid C, Karachi C, Leclercq D, Lafon C, Chapelon JY, Capelle L, Cornu P, Sanson M, Hoang-Xuan K, Delattre JY, Idbaih A. Clinical trial of blood-brain barrier disruption by pulsed ultrasound. Sci Transl Med. 2016 Jun 15;8(343):343re2. doi: 10.1126/scitranslmed.aaf6086.

  PMID: 27306666 BACKGROUND

• 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. 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. Lancet Oncol. 2023 May;24(5):509-522. doi: 10.1016/S1470-2045(23)00112-2.

  PMID: 37142373 DERIVED

Related Links

• CarThera

MeSH Terms

Conditions

Glioblastoma

Interventions

Carboplatin

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Ahmed IDBAIH, MD

  APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2018
• First Posted: November 16, 2018
• Study Start: February 18, 2019
• Primary Completion: June 23, 2021
• Study Completion: June 30, 2022
• Last Updated: September 7, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4); US (2)