GlioblastomaPhase 1/2SONOCLOUDNCT02253212
Safety of BBB Opening With the SonoCloud
A Phase 1/2 study testing SonoCloud and Carboplatin in people with Glioblastoma and Glioma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
PURPOSE: The purpose of this study is to determine whether transient opening of the blood-brain barrier by pulsed ultrasound using the SonoCloud implantable ultrasound device is safely tolerated in patients with recurrent glioblastoma immediately before systemic delivery of carboplatin-based chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Glioma, Brain Tumor
- What is being tested?
- SonoCloud and Carboplatin
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteFrance
- Study dates
- Jul 2014to Jul 2018
- 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 greater than 18 years.
- Subjects with recurrent glioma who have failed standard therapy with surgery and/or treatment with radiation and temozolomide.
- Patient eligible for Carboplatin-based chemotherapy
- Contrast-enhanced tumor less than 35 mm in diameter
- No risk of cerebral herniation
- Able to tolerate pre/post procedure steroid treatment
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- Social security affiliated (in France)
- Able and willing to give signed and informed consent
- Normal biological status
- Hemoglobin ≥ 10 g/dl
- Platelets ≥ 100000/mm3
- Neutrophils ≥ 1500/mm3
- Normal creatine clearance ≥ 60ml/mn
- ASAT < 3 N
- ALAT < 3 N
- Normal Bilirubin Level < 1.5 N
- Alkaline Phosphatase < 3 N
- INR < 1.5
- Prothrombin Level ≥ 70%
Who cannot join
- Allergic to Iodine, Gadolinium, Xylocain
- Contra-indications to echographic contrast agent (microbubbles)
- Severe Renal insufficiency
- Hepatic insufficiency
- Possible toxic treatment for CNS
- Previously infected surgical field
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- Uncontrolled epilepsy
- MRI contra-indications
- Hemostasis troubles thrombopenia <75.000, TP <60%, INR >1.5, anti-platelet or anticoagulant therapy on-going)
- Active phlebitis or active pulmonary embolism
- Pregnant or currently breast-feeding
- Patients under judicial protection
Trial locations and contacts
1 site in 1 country.
France1 site
Groupe Hospitalier Pitié Salpetriere - Neurosurgery Department
Paris, 75013
About this study
Official title: A Study to Evaluate the Safety of Transient Opening of the Blood-Brain Barrier by Low Intensity Pulsed Ultrasound With the SonoCloud Implantable Device in Patients With Recurrent Glioblastoma Before Chemotherapy Administration
PURPOSE: The purpose of this study is to determine whether transient opening of the blood-brain barrier by pulsed ultrasound using the SonoCloud implantable ultrasound device is safely tolerated in patients with recurrent glioblastoma immediately before systemic delivery of carboplatin-based chemotherapy.
STUDY HYPOTHESIS: The blood-brain barrier can be safely opened using pulsed ultrasound prior to chemotherapy administration in patients with recurrent glioblastoma. Transient opening of the blood-brain barrier by pulsed ultrasound will increase the glioblastoma exposure to carboplatin-based chemotherapy and increase progression-free and overall survival in patients with recurrent glioblastoma.
Read the detailed description
For patients with recurrent malignant gliomas, who have already been treated by a combination of surgery, radiation therapy and/or chemotherapy, few treatment options currently exist. Salvage therapies typically consist of systemic administration of chemotherapy agents, which have been shown to have limited effectiveness as median survival in this patient group is currently only 6 months.
One limitation to the efficacy of systemic chemotherapy in the treatment of brain tumors is the blood-brain barrier (BBB). To enhance the delivery of systemically administered chemotherapy agents to brain tumors, an implantable ultrasound device was developed that can be used to temporarily disrupt the BBB. Delivery of pulsed ultrasound, in combination with an ultrasound contrast agent, has been shown to temporarily disrupt the BBB for a duration of more than 6 hours and allow for a significantly increased penetration of systemically administered chemotherapy drugs in pre-clinical studies.
This study will evaluate the safety of temporary disruption of the BBB during carboplatin chemotherapy delivery in patients with recurrent glioblastoma. This study will also evaluate the maximum tolerated dose of ultrasound that can be used to disrupt the BBB.
The use of dynamic contrast-enhanced MRI will be evaluated for determining the extent and magnitude of BBB opening. Clinical efficacy (Survival) and radiological efficacy (Progression Free Survival) will also be evaluated as secondary endpoints.
- Conditions
- Glioblastoma, Glioma, Brain Tumor
- Being tested
- SonoCloud, Carboplatin
- Keywords
- Blood brain barrier (BBB), Disruption, Low intensity pulsed ultrasound (LIPU), Sonocloud device, Glioblastoma (GBM), Brain Cancer, Carboplatin, Therapeutic Ultrasound
- Medical subject headings
- Glioblastoma, Glioma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SonoCloudDevice
SonoCloud : dose escalation
CarboplatinDrug
Carboplatin : min 6 cycles - individual dose determination according to renal function and AUC
| Study group | Role | What they receive |
|---|---|---|
| SonoCloud + carboplatin | Experimental | SonoCloud : dose escalation Carboplatin : min 6 cycles - individual dose determination according to renal function and AUC Receives: Device: SonoCloud; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of transient disruption of the blood-brain barrier using the SonoCloud system in patients with recurrent glioblastoma.
Measured: 12 months
Secondary outcomes (4)
Maximum tolerated dose of ultrasound with the SonoCloud system for transient disruption of the BBB.
Measured: 12 months
Quantification of the disruption of the BBB by the SonoCloud system using dynamic T1 contrast-enhanced MRI.
Measured: 12 months
Progression-free survival in patients treated with the SonoCloud system in combination with carboplatin chemotherapy.
Measured: 12 months
Overall survival in patients treated with the SonoCloud system in combination with carboplatin chemotherapy.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2014 (estimated)
- Study startJul 2014
- Primary completionJul 2018
- Study completionJul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ahmed Idbaih, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02253212
- Sponsor's protocol ID
- P120905
- Other IDs
- 2014-000393-19, 2014
- Acronym
- SONOCLOUD
- Status last verified
- Oct 2018
- First submitted
- 29 Sep 2014
- Last updated
- 12 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Asquier N, Bouchoux G, Canney M, Martin C, Law-Ye B, Leclercq D, Chapelon JY, Lafon C, Idbaih A, Carpentier A. Blood-brain barrier disruption in humans using an implantable ultrasound device: quantification with MR images and correlation with local acoustic pressure. J Neurosurg. 2019 Feb 1;132(3):875-883. doi: 10.3171/2018.9.JNS182001. Print 2020 Mar 1.
PubMed 30717050Goldwirt L, Canney M, Horodyckid C, Poupon J, Mourah S, Vignot A, Chapelon JY, Carpentier A. Enhanced brain distribution of carboplatin in a primate model after blood-brain barrier disruption using an implantable ultrasound device. Cancer Chemother Pharmacol. 2016 Jan;77(1):211-6. doi: 10.1007/s00280-015-2930-5. Epub 2015 Dec 8.
PubMed 26645405
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Evaluate the Safety of Transient Opening of the Blood-Brain Barrier by Low Intensity Pulsed Ultrasound With the SonoCloud Implantable Device in Patients With Recurrent Glioblastoma Before Chemotherapy Administration
- ClinicalTrials.gov ID
- NCT02253212
- Acronym / sponsor ID
- SONOCLOUD / P120905
- Conditions
- Glioblastoma, Glioma, Brain Tumor
- Keywords
- Blood brain barrier (BBB), Disruption, Low intensity pulsed ultrasound (LIPU), Sonocloud device, Glioblastoma (GBM), Brain Cancer, Carboplatin, Therapeutic Ultrasound
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Jul 2014 (actual)
- Primary completion
- Jul 2018 (actual)
- Study completion
- Jul 2018 (actual)
- First posted
- 1 Oct 2014 (estimated)
- 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.
PURPOSE: The purpose of this study is to determine whether transient opening of the blood-brain barrier by pulsed ultrasound using the SonoCloud implantable ultrasound device is safely tolerated in patients with recurrent glioblastoma immediately before systemic delivery of carboplatin-based chemotherapy.
STUDY HYPOTHESIS: The blood-brain barrier can be safely opened using pulsed ultrasound prior to chemotherapy administration in patients with recurrent glioblastoma. Transient opening of the blood-brain barrier by pulsed ultrasound will increase the glioblastoma exposure to carboplatin-based chemotherapy and increase progression-free and overall survival in patients with recurrent glioblastoma.
Detailed description
For patients with recurrent malignant gliomas, who have already been treated by a combination of surgery, radiation therapy and/or chemotherapy, few treatment options currently exist. Salvage therapies typically consist of systemic administration of chemotherapy agents, which have been shown to have limited effectiveness as median survival in this patient group is currently only 6 months.
One limitation to the efficacy of systemic chemotherapy in the treatment of brain tumors is the blood-brain barrier (BBB). To enhance the delivery of systemically administered chemotherapy agents to brain tumors, an implantable ultrasound device was developed that can be used to temporarily disrupt the BBB. Delivery of pulsed ultrasound, in combination with an ultrasound contrast agent, has been shown to temporarily disrupt the BBB for a duration of more than 6 hours and allow for a significantly increased penetration of systemically administered chemotherapy drugs in pre-clinical studies.
This study will evaluate the safety of temporary disruption of the BBB during carboplatin chemotherapy delivery in patients with recurrent glioblastoma. This study will also evaluate the maximum tolerated dose of ultrasound that can be used to disrupt the BBB.
The use of dynamic contrast-enhanced MRI will be evaluated for determining the extent and magnitude of BBB opening. Clinical efficacy (Survival) and radiological efficacy (Progression Free Survival) will also be evaluated as secondary endpoints.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SonoCloud + carboplatin | Experimental | Device: SonoCloud, Drug: CarboplatinSonoCloud : dose escalation Carboplatin : min 6 cycles - individual dose determination according to renal function and AUC |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Age greater than 18 years.
- Subjects with recurrent glioma who have failed standard therapy with surgery and/or treatment with radiation and temozolomide.
- Patient eligible for Carboplatin-based chemotherapy
- Contrast-enhanced tumor less than 35 mm in diameter
- No risk of cerebral herniation
Key exclusion criteria (12 listed)
- Allergic to Iodine, Gadolinium, Xylocain
- Contra-indications to echographic contrast agent (microbubbles)
- Severe Renal insufficiency
- Hepatic insufficiency
- Possible toxic treatment for CNS
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 |
|---|---|---|
| SonoCloudSonoCloud : dose escalation | Device | SonoCloud + carboplatin |
| CarboplatinCarboplatin : min 6 cycles - individual dose determination according to renal function and AUC | Drug | SonoCloud + carboplatin |
Primary outcome
Safety of transient disruption of the blood-brain barrier using the SonoCloud system in patients with recurrent glioblastoma.
Time frame: 12 months
4 secondary outcomes
Maximum tolerated dose of ultrasound with the SonoCloud system for transient disruption of the BBB.
Time frame: 12 months
Quantification of the disruption of the BBB by the SonoCloud system using dynamic T1 contrast-enhanced MRI.
Time frame: 12 months
Progression-free survival in patients treated with the SonoCloud system in combination with carboplatin chemotherapy.
Time frame: 12 months
Overall survival in patients treated with the SonoCloud system in combination with carboplatin chemotherapy.
Time frame: 12 months
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 12 Oct 2018.
- Derived from this study: PubMed 30717050Asquier N, Bouchoux G, Canney M, Martin C, Law-Ye B, Leclercq D, Chapelon JY, Lafon C, Idbaih A, Carpentier A. Blood-brain barrier disruption in humans using an implantable ultrasound device: quantification with MR images and correlation with local acoustic pressure. J Neurosurg. 2019 Feb 1;132(3):875-883. doi: 10.3171/2018.9.JNS182001. Print 2020 Mar 1.
- Derived from this study: PubMed 26645405Goldwirt L, Canney M, Horodyckid C, Poupon J, Mourah S, Vignot A, Chapelon JY, Carpentier A. Enhanced brain distribution of carboplatin in a primate model after blood-brain barrier disruption using an implantable ultrasound device. Cancer Chemother Pharmacol. 2016 Jan;77(1):211-6. doi: 10.1007/s00280-015-2930-5. Epub 2015 Dec 8.
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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, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SonoCloud and Carboplatin in people with Glioblastoma and Glioma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 19 inclusion and 12 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 12 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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?
Safety of transient disruption of the blood-brain barrier using the SonoCloud system in patients with recurrent glioblastoma. (time frame: 12 months). 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 NCT02253212, which also lists 2 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 12 Oct 2018.