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

Glioblastoma, Adult Clinical Trial

— SC9-GBM-01  

Official title:

A Study to Evaluate the Safety and the Efficacy of Transient Opening of the Blood-brain Barrier (BBB) by Low Intensity Pulsed Ultrasound With the SonoCloud-9 Implantable Device in Recurrent Glioblastoma Patients Eligible for Surgery and for Carboplatin Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03744026
• Other study ID #: SC9-GBM-01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 18, 2019
• Est. completion date: June 30, 2022

Study information

• Verified date: September 2022
• Source: CarThera
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: June 30, 2022
• Est. primary completion date: June 23, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma, Adult

Intervention

Device:
• SonoCloud-9
Escalating numbers of ultrasound beams at constant acoustic pressure

Drug:
• Carboplatin
Dose of carboplatin infusion is AUC4-6

Locations

Country	Name	City	State
France	CHU	Angers
France	Hôpital Neurologique Pierre Wertheimer	Bron
France	Hôpital de La Timone	Marseille
France	Hôpital de la Pitié-Salpêtrière	Paris
United States	Northwestern University	Chicago	Illinois
United States	MD Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
CarThera

Countries where clinical trial is conducted

United States,  France, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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)

External Links

•   CarThera