Sonocloud-9 in Association With Carboplatin Versus Standard-of-Care Chemotherapies (CCNU or TMZ) in Recurrent GBM

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified July 2026 by CarThera
Sponsor
CarThera
Information Provided by (Responsible Party)
CarThera
Clinicaltrials.gov Identifier
NCT05902169
Other Study ID Numbers:
SC9-GBM-03
First Submitted
June 4, 2023
First Posted
June 12, 2023
Last Update Posted
August 17, 2026
Last Verified
July 2026

ClinicalTrials.gov processed this data on August 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
GlioblastomaRecurrent GlioblastomaGBM
Device: SonoCloud-9 (SC9)Drug: Lomustine

Study Design

Study TypeInterventional
Actual Enrollment560 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA 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.
Study Start DateJanuary 28, 2024
Actual Primary Completion Date1yr 5mos from now
Actual Study Completion Date1yr 10mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Experimental Arm: SonoCloud-9 Ultrasound + Carboplatin
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.
Device: SonoCloud-9 (SC9)
Implantation of SC9 device and repeat activation at constant acoustic pressure
Control Arm: SoC single agent chemotherapy TMZ or CCNU
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.
Drug: Lomustine
Dosed and administered per labelling.

Outcome Measures

Primary Outcome Measures
  1. 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).
Secondary Outcome Measures
  1. 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).
  2. 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.
  3. Overall survival at 12 months (OS12)
    Defined as the proportion of participants alive at 12 months
  4. Overall survival at 18 months (OS18)
    Defined as the proportion of participants alive at 18 months
  5. 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.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
1. Histologically proven glioblastoma (WHO criteria 2021), absence of IDH mutation demonstrated by negative IDH1 R132H staining on Immunohistochemistry. 2. Patient must have received prior first line therapy that must have contained both: 1. 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) 2. One line of maintenance chemotherapy and/or immune- or biological therapy, (with or without Tumor-Treating Fields) 3. First, unequivocal disease progression with 1. measurable tumor (\>100 mm2 or 1 cm3, based on RANO criteria) documented (e.g., increase of 25% in tumor diameter) on MRI and, 2. 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 4. Patient is a candidate for craniotomy and at least 50% resection of enhancing region 5. 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) 6. WHO performance status ≤ 2 (equivalent to Karnofsky Performance Status (KPS) ≥ 70) 7. Age ≥ 18 years 8. 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: 1. ≥ 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) 2. ≥ 6 weeks of prior bevacizumab 9. Adequate hematologic, hepatic, and renal laboratory values within 14 days prior to inclusion§ i.e.: 1. Hemoglobin ≥ 10 g/dL, platelets ≥ 100,000/mm3, neutrophils ≥ 1500/mm3. 2. Liver function test with ≤ grade 1 alterations, except if due to antiepileptic drug therapy or isolated increased bilirubin due to Gilbert syndrome 3. Estimated glomerular filtration rate (eGFR) of at least 60 mL/min/m2 using Appendix 12.4 formula 4. AST(SGOT)/ALT(SPGT) ≤ 3 X institutional ULN (upper Limit of Normal) 10. Patient able to understand clinical trial information and willing to provide signed and informed consent 11. 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 12. 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. 13. 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: 1. Multifocal enhancing tumor on T1w (unless all localized in a 5 cm diameter area) 2. Posterior fossa tumor 3. Known BRAF/ NTKR mutated patients 4. 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) 5. 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. 6. Contra-indication to carboplatin, CCNU or TMZ 7. Known history of hypersensitivity reactions to perflutren lipid microsphere components or to any of the inactive ingredients in ultrasound resonator 8. Patient has received bevacizumab for other reasons (such as tumor progression) than treating edema 9. Peripheral neuropathy or neuropathy ≥ grade 2 10. Uncontrolled epilepsy or evidence of intracranial pressure 11. Patient with known intracranial aneurism or having presented intra-tumor significant spontaneous hemorrhage 12. Patient with unremovable coils, clips, shunts, intravascular stents, and/or wafer, or reservoirs 13. 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. 14. Patient receiving enzyme-inducing antiepileptic drugs (namely phenytoin, carbamazepine and derivatives, phenobarbital), unless switched on another antiepileptic regimen 15. 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 16. Patient with known or suspected active or chronic infections 17. 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 18. Known sensitivity/allergy to gadolinium, or other intravascular contrast agents 19. Patient with impaired thermo-regulation or temperature sensation 20. Pregnant, or breastfeeding patient 21. 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 22. Patients under guardianship, curatorship, under legal protection or deprived of liberty by an administrative or judicial decision
Exclusion Criteria
Inclusion Criteria: 1. Histologically proven glioblastoma (WHO criteria 2021), absence of IDH mutation demonstrated by negative IDH1 R132H staining on Immunohistochemistry. 2. Patient must have received prior first line therapy that must have contained both: 1. 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) 2. One line of maintenance chemotherapy and/or immune- or biological therapy, (with or without Tumor-Treating Fields) 3. First, unequivocal disease progression with 1. measurable tumor (\>100 mm2 or 1 cm3, based on RANO criteria) documented (e.g., increase of 25% in tumor diameter) on MRI and, 2. 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 4. Patient is a candidate for craniotomy and at least 50% resection of enhancing region 5. 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) 6. WHO performance status ≤ 2 (equivalent to Karnofsky Performance Status (KPS) ≥ 70) 7. Age ≥ 18 years 8. 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: 1. ≥ 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) 2. ≥ 6 weeks of prior bevacizumab 9. Adequate hematologic, hepatic, and renal laboratory values within 14 days prior to inclusion§ i.e.: 1. Hemoglobin ≥ 10 g/dL, platelets ≥ 100,000/mm3, neutrophils ≥ 1500/mm3. 2. Liver function test with ≤ grade 1 alterations, except if due to antiepileptic drug therapy or isolated increased bilirubin due to Gilbert syndrome 3. Estimated glomerular filtration rate (eGFR) of at least 60 mL/min/m2 using Appendix 12.4 formula 4. AST(SGOT)/ALT(SPGT) ≤ 3 X institutional ULN (upper Limit of Normal) 10. Patient able to understand clinical trial information and willing to provide signed and informed consent 11. 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 12. 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. 13. 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: 1. Multifocal enhancing tumor on T1w (unless all localized in a 5 cm diameter area) 2. Posterior fossa tumor 3. Known BRAF/ NTKR mutated patients 4. 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) 5. 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. 6. Contra-indication to carboplatin, CCNU or TMZ 7. Known history of hypersensitivity reactions to perflutren lipid microsphere components or to any of the inactive ingredients in ultrasound resonator 8. Patient has received bevacizumab for other reasons (such as tumor progression) than treating edema 9. Peripheral neuropathy or neuropathy ≥ grade 2 10. Uncontrolled epilepsy or evidence of intracranial pressure 11. Patient with known intracranial aneurism or having presented intra-tumor significant spontaneous hemorrhage 12. Patient with unremovable coils, clips, shunts, intravascular stents, and/or wafer, or reservoirs 13. 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. 14. Patient receiving enzyme-inducing antiepileptic drugs (namely phenytoin, carbamazepine and derivatives, phenobarbital), unless switched on another antiepileptic regimen 15. 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 16. Patient with known or suspected active or chronic infections 17. 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 18. Known sensitivity/allergy to gadolinium, or other intravascular contrast agents 19. Patient with impaired thermo-regulation or temperature sensation 20. Pregnant, or breastfeeding patient 21. 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 22. Patients under guardianship, curatorship, under legal protection or deprived of liberty by an administrative or judicial decision Exclusion Criterion: 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.

Contacts and Locations

Sponsors and CollaboratorsCarThera
Locations
Mayo Clinic Arizona | Phoenix Arizona, United States, 805054Kaiser Permanente | Los Angeles California, United States, 90027UCLA | Los Angeles California, United States, 90095Sutter Health - California Pacific Medical Center | San Francisco California, United States, 94109University of California, San Francisco | San Francisco California, United States, 94143UCHealth | Aurora Colorado, United States, 80011Mayo Clinic of Jacksonville Florida | Jacksonville Florida, United States, 32224Miami Cancer Institute | Miami Florida, United States, 33176Moffitt Cancer Center | Tampa Florida, United States, 33612Winship Cancer Institute at Emory University | Atlanta Georgia, United States, 30322Northwestern University | Chicago Illinois, United States, 60611Indiana University Health | Indianapolis Indiana, United States, 46202John Hopkins University | Baltimore Maryland, United States, 21287Mayo Clinic Rochester | Rochester Minnesota, United States, 55905Weill Cornell Medicine | New York New York, United States, 10021NewYork-Presbyterian / Columbia University Irving Medical Center | New York New York, United States, 10032Lennox Hill Hospital | New York New York, United States, 10075University of North Carolina | Chapel Hill North Carolina, United States, 27516Neurological Institute Brain Tumor Centre Taussig Cancer Cente | Cleveland Ohio, United States, 44106Penn State Health Milton S. Hershey Medical Center | Hershey Pennsylvania, United States, 17033University of Texas Southwestern Medical Center | Dallas Texas, United States, 75390University of Texas Houston Health Science Center | Houston Texas, United States, 77030University of Utah, Hunstman Cancer Institute | Salt Lake City Utah, United States, 84112Medizinische Universitaet Innsbruck | Innsbruck , Austria, 6020Universitair Ziekenhuis Brussel | Brussels , Belgium, Universitair Ziekenhuis Leuven | Leuven , Belgium, CHU de Liège | Liège , Belgium, Rigshospitalet | Copenhagen , Denmark, 2100Odense University Hospital | Odense , Denmark, 5000Hôpital Neurologique Pierre Wertheimer | Bron , France, Hôpital de La Timone | Marseille , France, Hôpital de la Pitié-Salpêtrière | Paris , France, Hôpital Foch | Suresnes , France, 92150Charité Universitätsmedizin Berlin | Berlin , Germany, 10117Klinikum Chemnitz gGmbH | Chemnitz , Germany, 09113Neurochirurgie uniklinik Köln | Cologne , Germany, Universitätsklinikum Carl Gustav Carus Dresden | Dresden , Germany, 01307Universitätsklinikum Essen Klinik für Neurologie | Essen , Germany, 45147Ospedale Bellaria | Bologna , Italy, 40139Ospedale Civile di Livorno | Livorno , Italy, 57124Istituto Oncologico Veneto | Padua , Italy, IFO - Istituto Nazionale Tumori Regina Elena | Roma , Italy, Irccs Istituto Clinico Humanitas | Rozzano , Italy, 20089Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino | Torino , Italy, 10126Erasmus Medisch Centrum (Erasmus MC) | Rotterdam , Netherlands, Haaglanden Medisch Centrum | The Hague , Netherlands, 2263Vall d'Hebron Institute of Oncology (VHIO) | Barcelona , Spain, 08035Hospital Clinic de Barcelona | Barcelona , Spain, 08036Hospital Universitario HM Sanchinarro | Madrid , Spain, 28050Hospital Universitario 12 de Octubre | Madrid , Spain, Hospital Universitario Virgen del Rocío | Seville , Spain, 41013Sahlgrenska University Hospital | Gothenburg , Sweden, 413 45Akademiska sjukhuset | Uppsala , Sweden, 75185Inselspital Bern | Bern , Switzerland, 3010Centre Hospitalier Universitaire Vaudois (CHUV) | Lausanne , Switzerland, 1011