GlioblastomaPhase 3SONOBIRDNCT05902169
Sonocloud-9 in Association With Carboplatin Versus Standard-of-Care Chemotherapies (CCNU or TMZ) in Recurrent GBM
A Phase 3 study testing SonoCloud-9 (SC9), Carboplatin and Lomustine in people with Glioblastoma and Recurrent Glioblastoma, run by CarThera at 56 sites in 11 countries.
Trial summary
The brain is protected from any toxic or inflammatory molecule by the blood-brain barrier (BBB). This physical barrier is located at the level of the blood vessel walls. Because of these barrier properties, the blood vessels are also impermeable to the passage of therapeutic molecules from the blood to the brain. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Recurrent Glioblastoma, GBM
- What is being tested?
- SonoCloud-9 (SC9), Carboplatin and Lomustine
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 560 participants
- Where
- 56 sitesin 11 countries
- Study dates
- 29 Jan 2024to 30 Jun 2028
- Phase
- Phase 3
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
- Histologically proven glioblastoma (WHO criteria 2021), absence of IDH mutation demonstrated by negative IDH1 R132H staining on Immunohistochemistry.
- Patient must have received prior first line therapy that must have contained both:
- Prior surgery or biopsy and standard fractionated radiotherapy (1.8-2 Gy/fraction, ≥56 Gy<66 Gy) or hypofractionated radiotherapy (15 x 2.66 Gy or similar regimen)
- One line of maintenance chemotherapy and/or immune- or biological therapy, (with or without Tumor-Treating Fields)
- First, unequivocal disease progression with
- measurable tumor (>100 mm2 or 1 cm3, based on RANO criteria) documented (e.g., increase of 25% in tumor diameter) on MRI and,
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- interval of a minimum of 12 weeks since the completion of prior radiotherapy, unless there is a new lesion outside the radiation field or unequivocal evidence of viable tumor on histopathological sampling
- Patient is a candidate for craniotomy and at least 50% resection of enhancing region
- Maximal enhancing tumor diameter prior to inclusion ≤ 5 (+7%) cm on T1w on MRI performed within 14 days prior to inclusion§. (In case of planned lobectomy, post operative peritumoral brain or residual size ≤5 cm)
- WHO performance status ≤ 2 (equivalent to Karnofsky Performance Status (KPS) ≥ 70)
- Age ≥ 18 years
- Participant must be recovered from acute toxic effects (≤ grade 2) of all prior anticancer therapy. Interval since last therapy to presumed date of surgery of at least:
- ≥ 4 weeks or 5 half-lives (whichever is shorter) for
- Cytotoxic
- Other small chemical entity (e.g., targeted therapy)
- For biologics (e.g., antibodies, except bevacizumab)
- ≥ 6 weeks of prior bevacizumab
- Adequate hematologic, hepatic, and renal laboratory values within 14 days prior to inclusion§ i.e.:
- Hemoglobin ≥ 10 g/dL, platelets ≥ 100,000/mm3, neutrophils ≥ 1500/mm3.
- Liver function test with ≤ grade 1 alterations, except if due to antiepileptic drug therapy or isolated increased bilirubin due to Gilbert syndrome
- Estimated glomerular filtration rate (eGFR) of at least 60 mL/min/m2 using Appendix 12.4 formula
- AST(SGOT)/ALT(SPGT) ≤ 3 X institutional ULN (upper Limit of Normal)
- Patient able to understand clinical trial information and willing to provide signed and informed consent
- Patient of childbearing potential must have a negative pregnancy test within 14 days prior to inclusion§ and must agree to use a medically-acceptable method of birth control during the treatment period and, if randomized in the experimental arm, for at least 1 month after the last cycle of carboplatin
- A male patient must agree to use condoms during the treatment period and, if randomized in the experimental arm, for at least 3 months after the last cycle of carboplatin; the patient must also refrain from donating sperm during this period.
- Patient must be a beneficiary of a health plan that covers routine patient care costs. Patient must be a beneficiary of or affiliated with a social security scheme (according to country-specific requirements)
- (§) These exam/lab tests could be (re)evaluated before randomization if the corresponding selection criteria could not be fully met at time of inclusion. If not met before randomization, the patient will be considered as screen failure.
- Non-Inclusion Criteria:
- Multifocal enhancing tumor on T1w (unless all localized in a 5 cm diameter area)
- Posterior fossa tumor
- Known BRAF/ NTKR mutated patients
- Patient at risk of surgery site infection (e.g., 2 or more previous craniotomies/neurosurgery within the last 3 months, poor skin condition, known impaired wound healing and/or previously infected surgical field, uncontrolled diabetes or any other condition that is of increased infectious risk in the opinion of the neurosurgeon)
- Patient treated at high, stable -or average- dose of corticosteroids (≥ 6 mg/day dexamethasone or equivalent) in the 7 days prior to inclusion. Patients on dexamethasone for reasons other than mass effect may still be enrolled.
- Contra-indication to carboplatin, CCNU or TMZ
- Known history of hypersensitivity reactions to perflutren lipid microsphere components or to any of the inactive ingredients in ultrasound resonator
- Patient has received bevacizumab for other reasons (such as tumor progression) than treating edema
- Peripheral neuropathy or neuropathy ≥ grade 2
- Uncontrolled epilepsy or evidence of intracranial pressure
- Patient with known intracranial aneurism or having presented intra-tumor significant spontaneous hemorrhage
- Patient with unremovable coils, clips, shunts, intravascular stents, and/or wafer, or reservoirs
- Patient with medical need to be on continued anti-platelet aggregation therapy and/or anticoagulation. Patients for whom anticoagulation/platelet aggregation can be temporarily interrupted may be eligible after discussion and prior authorization by the sponsor.
- Patient receiving enzyme-inducing antiepileptic drugs (namely phenytoin, carbamazepine and derivatives, phenobarbital), unless switched on another antiepileptic regimen
- History of other malignancy within 3 years prior to study start with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma, non-melanomatous skin cancer or carcinoma in situ of the uterine cervix
- Patient with known or suspected active or chronic infections
- Patient with known significant cardiac disease, known to have right-to-left shunts, severe pulmonary hypertension (pulmonary artery pressure > 90 mm Hg), uncontrolled systemic hypertension, or acute respiratory distress syndrome
- Known sensitivity/allergy to gadolinium, or other intravascular contrast agents
- Patient with impaired thermo-regulation or temperature sensation
- Pregnant, or breastfeeding patient
- Any other serious patient medical or psychological condition that may interfere with adequate and safe delivery of treatment and care (e.g., positive human immunodeficiency virus [HIV] status, potential blood-borne infections, malnutrition…), circumstance (e.g., sinus opening during surgery), psychological, morphological characteristics (e.g., skin characteristics, bone thickness), or any pre-existing comorbidities that in the investigator's opinion may prevent the implantation of the device, may impair the ability of the patient to receive treatment with SonoCloud-9 or may be confounding for evaluation of the clinical trial endpoints
- Patients under guardianship, curatorship, under legal protection or deprived of liberty by an administrative or judicial decision
Who cannot join
- Occurrence of any major medical illnesses or impairments that in the Investigator's opinion may hampered the ability of the patient to receive treatment with SonoCloud-9 or may be confounding for evaluation of the clinical endpoints.
Trial locations and contacts
56 sites in 11 countries. Contact the study team or a site near you to ask about taking part.
56 sites in 11 countries
United States23 sites, 22 recruiting
- Recruiting
Winship Cancer Institute at Emory University
Atlanta, Georgia, 30322
Edjah Nduom, MD
- Recruiting
UCHealth
Aurora, Colorado, 80011
Kevin Lillehei, MD
- Recruiting
John Hopkins University
Baltimore, Maryland, 21287
Chetan Bettegowda, MD
- Recruiting
University of North Carolina
Chapel Hill, North Carolina, 27516
Carlos David, MD
- Recruiting
Northwestern University
Chicago, Illinois, 60611
Rimas Lukas, MD
- Recruiting
Neurological Institute Brain Tumor Centre Taussig Cancer Cente
Cleveland, Ohio, 44106
Matthew Grabowski, MD
- Recruiting
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Toral Patel, MD
- Recruiting
Penn State Health Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
Brad Zacharia, MD
- Recruiting
University of Texas Houston Health Science Center
Houston, Texas, 77030
Yoshua Esquenazi, MD
- Recruiting
Indiana University Health
Indianapolis, Indiana, 46202
Kathryn Nevel, MD
- Recruiting
Mayo Clinic of Jacksonville Florida
Jacksonville, Florida, 32224
Kaisorn Chaichana, MD
- Not yet recruiting
Kaiser Permanente
Los Angeles, California, 90027
Daniel Green, MD
- Not yet recruiting
UCLA
Los Angeles, California, 90095
Richard Everson, MD
- Recruiting
Miami Cancer Institute
Miami, Florida, 33176
Michael Mc Dermott, MD
- Recruiting
Weill Cornell Medicine
New York, New York, 10021
Rohan Ramakhrisna, MD
- Recruiting
NewYork-Presbyterian / Columbia University Irving Medical Center
New York, New York, 10032
Brian JA Gill, MD
212-342-5162, cancerclinicaltrials@cumc.columbia.edu
- Recruiting
Lennox Hill Hospital
New York, New York, 10075
Randy D'Amico, MD
- Recruiting
Mayo Clinic Arizona
Phoenix, Arizona, 805054
Maciej Mrugala, MD
- Active, not recruiting
Mayo Clinic Rochester
Rochester, Minnesota, 55905
- Recruiting
University of Utah, Hunstman Cancer Institute
Salt Lake City, Utah, 84112
Randy Jenssen, MD
- Recruiting
Sutter Health - California Pacific Medical Center
San Francisco, California, 94109
Lewis Leng, MD
- Recruiting
University of California, San Francisco
San Francisco, California, 94143
Nicholas Butowski, MD
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
James Liu, MD
Germany6 sites, 6 recruiting
- Recruiting
Charité Universitätsmedizin Berlin
Berlin, 10117
Martin Misch, MD
- Recruiting
Klinikum Chemnitz gGmbH
Chemnitz, 09113
Sven-Axel May, MD
- Recruiting
Neurochirurgie uniklinik Köln
Cologne
Roland Goldbrunner, MD
- Recruiting
Universitätsklinikum Carl Gustav Carus Dresden
Dresden, 01307
Dietmar Krex, MD
- Recruiting
Universitätsklinikum Essen Klinik für Neurologie
Essen, 45147
Sied Kebir, MD
- Recruiting
University Hospital Munster
Münster, 48149
Walter Stummer, MD
Italy6 sites, 6 recruiting
- Recruiting
Ospedale Bellaria
Bologna, 40139
Enrico Franceschi, MD
- Recruiting
Ospedale Civile di Livorno
Livorno, 57124
Anna Luisa Di Stefano, MD
- Recruiting
Istituto Oncologico Veneto
Padua
Giuseppe Lombardi, MD
- Recruiting
IFO - Istituto Nazionale Tumori Regina Elena
Roma
Veronica Villani, MD
- Recruiting
Irccs Istituto Clinico Humanitas
Rozzano, 20089
Matteo Simonelli, MD
- Recruiting
Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino
Torino, 10126
Roberta Ruda, MD
Spain5 sites, 5 recruiting
- Recruiting
Vall d'Hebron Institute of Oncology (VHIO)
Barcelona, 08035
Maria Vieito Villar, MD
- Recruiting
Hospital Clinic de Barcelona
Barcelona, 08036
Jose Juan Gonzalez Sanchez, MD
- Recruiting
Hospital Universitario HM Sanchinarro
Madrid, 28050
Juan Manuel Sepulveda Sanchez, MD
- Recruiting
Hospital Universitario 12 de Octubre
Madrid
Angel Perez-Nunez, MD
- Recruiting
Hospital Universitario Virgen del Rocío
Seville, 41013
Ignacio Martín Schrader, MD
France4 sites, 4 recruiting
- Recruiting
Hôpital Neurologique Pierre Wertheimer
Bron
François Ducray, MD
- Recruiting
Hôpital de La Timone
Marseille
Olivier Chinot, MD
- Recruiting
Hôpital de la Pitié-Salpêtrière
Paris
Ahmed Idbaih, MD
- Recruiting
Hôpital Foch
Suresnes, 92150
Nadia Younan, MD
Belgium3 sites, 3 recruiting
- Recruiting
Universitair Ziekenhuis Brussel
Brussels
Duerinck Johnny, MD
- Recruiting
Universitair Ziekenhuis Leuven
Leuven
Steven de Vleeschouwer, MD
- Recruiting
CHU de Liège
Liège
Pierre Frères, MD
Denmark2 sites, 2 recruiting
- Recruiting
Rigshospitalet
Copenhagen, 2100
Jane Skjøth-Rasmussen, MD
- Recruiting
Odense University Hospital
Odense, 5000
Frantz Rom Poulsen, MD
Netherlands2 sites, 2 recruiting
- Recruiting
Erasmus Medisch Centrum (Erasmus MC)
Rotterdam
Marjolein Geurts, MD
- Recruiting
Haaglanden Medisch Centrum
The Hague, 2263
Marike Broekman, MD
Sweden2 sites, 2 recruiting
- Recruiting
Sahlgrenska University Hospital
Gothenburg, 413 45
Louise Carstam, MD
- Recruiting
Akademiska sjukhuset
Uppsala, 75185
George Holgersson, MD
Switzerland2 sites, 2 recruiting
- Recruiting
Inselspital Bern
Bern, 3010
Philippe Schucht, MD
- Recruiting
Centre Hospitalier Universitaire Vaudois (CHUV)
Lausanne, 1011
Andreas Hottinger, MD
Austria1 site, 1 recruiting
- Recruiting
Medizinische Universitaet Innsbruck
Innsbruck, 6020
Christian Freyschlag, MD
About this study
Official title: A Randomized, Open-label, Multicentric, Two-arm Pivotal Trial of SonoCloud-9 Combined With Carboplatin (CBDCA) vs Standard of Care Lomustine (CCNU) or Temozolomide (TMZ) in Patients Undergoing Planned Resection for First Recurrence Glioblastoma.
The brain is protected from any toxic or inflammatory molecule by the blood-brain barrier (BBB). This physical barrier is located at the level of the blood vessel walls. Because of these barrier properties, the blood vessels are also impermeable to the passage of therapeutic molecules from the blood to the brain. The development of effective treatments against glioblastoma is thus limited due to the BBB that prevents most drugs injected in the bloodstream from getting into brain tissue where the tumour is seated. The SonoCloud-9 (SC9) is an investigational device using ultrasound technology and specially developed to open the BBB in the area of and surrounding the tumour. The transient opening of the BBB allows more drugs to reach the brain tumour tissue. Carboplatin is a chemotherapy that is approved to treat different cancer types alone or in combination with other drugs, and has been used in the treatment of glioblastoma. Despite its proven efficacy in the laboratory on glioblastoma cells, carboplatin does not readily cross the BBB in humans. A clinical trial has shown that in combination with the SonoCloud-9, more carboplatin can reach the brain tumour tissue. The objective of the proposed trial is to show that the association - carboplatin with the SonoCloud-9 - will increase efficacy of the drug in patients with recurrent glioblastoma.
- Conditions
- Glioblastoma, Recurrent Glioblastoma, GBM
- Being tested
- SonoCloud-9 (SC9), Carboplatin, Lomustine, Temozolomide
- Keywords
- carboplatin, SonoCloud, blood-brain barrier, 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-9 (SC9)Device
Implantation of SC9 device and repeat activation at constant acoustic pressure
CarboplatinDrug
Also called CycloButane DiCarboxylic Acid (CBDCA)
Dose of carboplatin AUC 5 mg/ml.min-1 calculated using Calvert's formula:
Dose (mg) = target AUC (mg/mL x minute) x [glomerular filtration rate (GFR) mL/minute + 25].
LomustineDrug
Also called 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)
Dosed and administered per labelling.
TemozolomideDrug
Also called Temodal
Dosed and administered per labelling.
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm: SonoCloud-9 Ultrasound + Carboplatin | Experimental | The SonoCloud-9 (SC9) device will be implanted in the skull bone window upon completion of tumor resection and routine craniotomy. Carboplatin (CBDCA) will be administered intravenously prior to sonication. The CBDCA/SC9 treatment will be repeated every 3 weeks (depending on patient's tolerability) until disease progression or as clinically indicated. Administration of up to 7 cycles is planned. Receives: Device: SonoCloud-9 (SC9); Drug: Carboplatin |
| Control Arm: SoC single agent chemotherapy TMZ or CCNU | Active comparator | Standard of Care (SoC) treatment with either temozolomide (TMZ) or lomustine (CCNU).
Standard TMZ chemotherapy as a single oral dose every 4 weeks for up to 6 cycles.
Standard CCNU chemotherapy as a single oral dose every 6 weeks for up to 4 cycles. Receives: Drug: Lomustine; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS)
Survival status will be collected during the treatment period, for up to 7 months (short-term follow-up) and then every 3 months as standard of care follow-up (long-term follow-up) until participant's 'End of Study', defined as end of survival follow-up period, death, withdrawal of consent for the collection of data, or 'lost to follow-up' (whichever comes first).
Measured: Up to 24 months
Secondary outcomes (5)
Tumor Growth Rate
Tumor Growth Rate will be determined by measuring hyperintense tumor volume using T1w contrast-enhancing tumor-related region from post-surgery MRI baseline to unequivocal progression MRI (i.e., suspected radiologic progression confirmed by repeat scan).
Measured: Up to week 24
Progression Free Survival (PFS)
Defined as the time from date of randomization to the earlier of the following events: unequivocal tumor progression as determined by IRC per RANO criteria or death due to any cause.
Measured: Up to 24 months
Overall survival at 12 months (OS12)
Defined as the proportion of participants alive at 12 months
Measured: 12 months
Overall survival at 18 months (OS18)
Defined as the proportion of participants alive at 18 months
Measured: 18 months
Progression-free survival at 6 months (PFS6)
Defined as the proportion of participants without disease progression or death due to any cause at 6 months.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2023
- Study start29 Jan 2024
- Primary completion28 Jan 2028 (estimated)
- Study completion30 Jun 2028 (estimated)
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.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 560 participants (estimated)
Sponsor and investigators
- Lead sponsor
- CarThera
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05902169
- Sponsor's protocol ID
- SC9-GBM-03
- Other IDs
- 2023-505829-14-00, 2023
- Acronym
- SONOBIRD
- Status last verified
- Aug 2026
- First submitted
- 5 Jun 2023
- Last updated
- 5 Oct 2026
- 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 27306666Sonabend 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