Glioblastoma, AdultPhase 1/2SC9-GBM-01NCT03744026
Safety and Efficacy of Transient Opening of the Blood-brain Barrier (BBB) With the SonoCloud-9
A Phase 1/2 study testing SonoCloud-9 and Carboplatin in people with Glioblastoma, Adult, run by CarThera at 6 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Adult
- What is being tested?
- SonoCloud-9 and Carboplatin
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 18 Feb 2019to 30 Jun 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
France4 sites
CHU
Angers
Hôpital Neurologique Pierre Wertheimer
Bron
Hôpital de La Timone
Marseille
Hôpital de la Pitié-Salpêtrière
Paris
United States2 sites
Northwestern University
Chicago, Illinois, 60611
MD Anderson Cancer Center
Houston, Texas, 77030
About this study
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
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.
Read the 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).
- Conditions
- Glioblastoma, Adult
- Being tested
- SonoCloud-9, Carboplatin
- Keywords
- Recurrent Glioblastoma, Carboplatin, Ultrasound, Blood-brain barrier, Glioblastoma, SonoCloud, Low Intensity Pulsed Ultrasound (LIPU)
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SonoCloud-9Device
Escalating numbers of ultrasound beams at constant acoustic pressure
CarboplatinDrug
Dose of carboplatin infusion is AUC4-6
| Study group | Role | What they receive |
|---|---|---|
| SonoCloud-9 Ultrasound + Carboplatin | Experimental | SonoCloud-9 Carboplatin: 6 cycles (every 4 weeks) Receives: Device: SonoCloud-9; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: At the end of the first three sonication treatments (treatment occurs every 4 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2018
- Study start18 Feb 2019
- Primary completion23 Jun 2021
- Study completion30 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- CarThera
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ahmed IDBAIH, MD, Principal investigator, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03744026
- Sponsor's protocol ID
- SC9-GBM-01
- Acronym
- SC9-GBM-01
- Status last verified
- Sep 2022
- First submitted
- 13 Nov 2018
- Last updated
- 7 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 27306666Carpentier 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. 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. Nat Commun. 2024 Feb 23;15(1):1650. doi: 10.1038/s41467-024-45818-7.
PubMed 38396134Sonabend 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.
PubMed 37142373
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03744026
- Acronym / sponsor ID
- SC9-GBM-01 / SC9-GBM-01
- Conditions
- Glioblastoma, Adult
- Keywords
- Recurrent Glioblastoma, Carboplatin, Ultrasound, Blood-brain barrier, Glioblastoma, SonoCloud, Low Intensity Pulsed Ultrasound (LIPU)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- CarTheraIndustry (pharma, biotech, devices)
- Study start
- 18 Feb 2019 (actual)
- Primary completion
- 23 Jun 2021 (actual)
- Study completion
- 30 Jun 2022 (actual)
- First posted
- 16 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SonoCloud-9 Ultrasound + Carboplatin | Experimental | Device: SonoCloud-9, Drug: CarboplatinSonoCloud-9 Carboplatin: 6 cycles (every 4 weeks) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age ≥ 18 years, able and willing to give signed and informed consent.
- Patient with histologically proven recurrent de novo GBM:
- Patient eligible for carboplatin-based chemotherapy.
- Patient eligible for a surgical resection.
- Maximal tumor diameter at inclusion (pre surgery) ≤ 70 mm in T1wMRI.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SonoCloud-9Escalating numbers of ultrasound beams at constant acoustic pressure | Device | SonoCloud-9 Ultrasound + Carboplatin |
| CarboplatinDose of carboplatin infusion is AUC4-6 | Drug | SonoCloud-9 Ultrasound + Carboplatin |
Primary outcome
Dose limiting toxicity (DLT) of number of activated ultrasound beams
Time frame: 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
Time frame: 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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2022.
- Background: PubMed 27306666Carpentier 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.
- Derived from this study: PubMed 38396134Carpentier 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. 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. Nat Commun. 2024 Feb 23;15(1):1650. doi: 10.1038/s41467-024-45818-7.
- Derived from this study: PubMed 37142373Sonabend 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.
- CarTheraLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Glioblastoma, Adult
RecruitingPhase 1
A Phase 1 Safety and Dose Finding Study of GLIX1 in Adults With Recurrent or Progressive High-grade Glioma
Glioblastoma Multiforme of Brain, Glioma
RecruitingPhase 1
A Study of RNA-lipid Particle (RNA-LP) Vaccines for Newly Diagnosed Pediatric High-Grade Gliomas (pHGG) and Adult Glioblastoma (GBM)
Adult Glioblastoma, High Grade Glioma
Not yet recruitingPhase 1/2
A Study of SRN-101 Gene Therapy in Adults With Recurrent High-Grade Glioma (ALERT-1)
Recurrent High Grade Gliomas, Glioblastoma (GBM)
RecruitingPhase 1/2
A Study of Zedoresertib (Debio 0123) in Combination With Temozolomide in Adult Participants With Recurrent or Progressive Glioblastoma and of Zedoresertib (Debio 0123) in Combination With Temozolomide and Radiotherapy in Adult Participants With Newly Diagnosed Glioblastoma
Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype, Astrocytoma, Grade III
Active, not recruitingPhase 1
A Trial of Belzutifan (PT2977, MK-6482) Tablets In Patients With Advanced Solid Tumors (MK-6482-001)
Advanced Solid Tumors, Solid Tumor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ahmed IDBAIH, MD principal investigator
APHP
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SonoCloud-9 and Carboplatin in people with Glioblastoma, Adult, run by CarThera at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in France, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicity (DLT) of number of activated ultrasound beams (time frame: 15 days after the first sonication treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03744026, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2022.