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Safety and Efficacy of Transient Opening of the Blood-brain Barrier (BBB) With the SonoCloud-9 (SC9-GBM-01)

Primary Purpose

Glioblastoma, Adult

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

SonoCloud-9

Carboplatin

About this trial

This is an interventional treatment trial for Glioblastoma, Adult focused on measuring Recurrent Glioblastoma, Carboplatin, Ultrasound, Blood-brain barrier, Glioblastoma, SonoCloud, Low Intensity Pulsed Ultrasound (LIPU)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

Age ≥ 18 years, able and willing to give signed and informed consent.
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.*
Patient eligible for carboplatin-based chemotherapy.
Patient eligible for a surgical resection.
Maximal tumor diameter at inclusion (pre surgery) ≤ 70 mm in T1wMRI.
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.

Key Exclusion Criteria:

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.

Sites / Locations

Northwestern University
MD Anderson Cancer Center
CHU
Hôpital Neurologique Pierre Wertheimer
Hôpital de La Timone
Hôpital de la Pitié-Salpêtrière

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SonoCloud-9 Ultrasound + Carboplatin

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Blood-Brain Barrier (BBB) opening

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

Secondary Outcome Measures

Full Information

NCT ID

NCT03744026

First Posted

November 13, 2018

Last Updated

September 6, 2022

Sponsor

CarThera

1. Study Identification

Unique Protocol Identification Number

NCT03744026

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Completed

Study Start Date

February 18, 2019 (Actual)

Primary Completion Date

June 23, 2021 (Actual)

Study Completion Date

June 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

CarThera

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma, Adult

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

38 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SonoCloud-9 Ultrasound + Carboplatin

Arm Type

Experimental

Arm Description

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

Intervention Type

Device

Intervention Name(s)

SonoCloud-9

Intervention Description

Escalating numbers of ultrasound beams at constant acoustic pressure

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Intervention Description

Dose of carboplatin infusion is AUC4-6

Primary Outcome Measure Information:

Title

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

Description

Time Frame

15 days after the first sonication treatment

Title

Blood-Brain Barrier (BBB) opening

Description

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

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: 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. Maximal tumor diameter at inclusion (pre surgery) ≤ 70 mm in T1wMRI. 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. Key Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ahmed IDBAIH, MD

Organizational Affiliation

APHP

Official's Role

Principal Investigator

Facility Information:

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

CHU

City

Angers

Country

France

Facility Name

Hôpital Neurologique Pierre Wertheimer

City

Bron

Country

France

Facility Name

Hôpital de La Timone

City

Marseille

Country

France

Facility Name

Hôpital de la Pitié-Salpêtrière

City

Paris

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

27306666

Citation

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.

Results Reference

background

Links:

URL

http://www.carthera.eu

Description

CarThera

Learn more about this trial

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

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