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Sonocloud-9 i samband med Carboplatin Versus Standard-of-Care kemoterapier (CCNU eller TMZ) vid återkommande GBM (SONOBIRD)

4 november 2026 uppdaterad av: CarThera

En randomiserad, öppen, multicentrisk, tvåarmad pivotal studie av SonoCloud-9 kombinerat med Carboplatin (CBDCA) vs Standard of Care Lomustine (CCNU) eller Temozolomide (TMZ) hos patienter som genomgår planerad resektion för första recidiv av glioblastom.

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.

Studieöversikt

Status

Aktiv, inte rekryterande

Betingelser

Intervention / Behandling

Studietyp

Interventionell

Inskrivning (Beräknad)

560

Fas

  • Fas 3

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Belgien
      • Brussels, Belgien
        • Universitair Ziekenhuis Brussel
      • Leuven, Belgien
        • Universitair Ziekenhuis Leuven
      • Liège, Belgien
        • CHU de Liège
  • Danmark
      • Copenhagen, Danmark, 2100
        • Rigshospitalet
      • Odense, Danmark, 5000
        • Odense University Hospital
  • Frankrike
      • Bron, Frankrike
        • Hôpital Neurologique Pierre Wertheimer
      • Marseille, Frankrike
        • Hôpital de La Timone
      • Paris, Frankrike
        • Hôpital de la Pitié-Salpêtrière
      • Suresnes, Frankrike, 92150
        • Hôpital Foch
  • Förenta staterna
    • Arizona
      • Phoenix, Arizona, Förenta staterna, 805054
        • Mayo Clinic Arizona
    • California
      • Los Angeles, California, Förenta staterna, 90095
        • UCLA
      • Los Angeles, California, Förenta staterna, 90027
        • Kaiser Permanente
      • San Francisco, California, Förenta staterna, 94143
        • University of California, San Francisco
      • San Francisco, California, Förenta staterna, 94109
        • Sutter Health - California Pacific Medical Center
    • Colorado
      • Aurora, Colorado, Förenta staterna, 80011
        • UCHealth
    • Florida
      • Jacksonville, Florida, Förenta staterna, 32224
        • Mayo Clinic of Jacksonville Florida
      • Miami, Florida, Förenta staterna, 33176
        • Miami Cancer Institute
      • Tampa, Florida, Förenta staterna, 33612
        • Moffitt Cancer Center
    • Georgia
      • Atlanta, Georgia, Förenta staterna, 30322
        • Winship Cancer Institute at Emory University
    • Illinois
      • Chicago, Illinois, Förenta staterna, 60611
        • Northwestern University
    • Indiana
      • Indianapolis, Indiana, Förenta staterna, 46202
        • Indiana University Health
    • Maryland
      • Baltimore, Maryland, Förenta staterna, 21287
        • John Hopkins University
    • Minnesota
      • Rochester, Minnesota, Förenta staterna, 55905
        • Mayo Clinic Rochester
    • New York
      • New York, New York, Förenta staterna, 10021
        • Weill Cornell Medicine
      • New York, New York, Förenta staterna, 10075
        • Lennox Hill Hospital
      • New York, New York, Förenta staterna, 10032
        • NewYork-Presbyterian / Columbia University Irving Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, Förenta staterna, 27516
        • University of North Carolina
    • Ohio
      • Cleveland, Ohio, Förenta staterna, 44106
        • Neurological Institute Brain Tumor Centre Taussig Cancer Cente
    • Pennsylvania
      • Hershey, Pennsylvania, Förenta staterna, 17033
        • Penn State Health Milton S. Hershey Medical Center
    • Texas
      • Dallas, Texas, Förenta staterna, 75390
        • University of Texas Southwestern Medical Center
      • Houston, Texas, Förenta staterna, 77030
        • University of Texas Houston Health Science Center
    • Utah
      • Salt Lake City, Utah, Förenta staterna, 84112
        • University of Utah, Hunstman Cancer Institute
  • Italien
      • Bologna, Italien, 40139
        • Ospedale Bellaria
      • Livorno, Italien, 57124
        • Ospedale Civile di Livorno
      • Padua, Italien
        • Istituto Oncologico Veneto
      • Roma, Italien
        • IFO - Istituto Nazionale Tumori Regina Elena
      • Rozzano, Italien, 20089
        • Irccs Istituto Clinico Humanitas
      • Torino, Italien, 10126
        • Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino
  • Nederländerna
      • Rotterdam, Nederländerna
        • Erasmus Medisch Centrum (Erasmus MC)
      • The Hague, Nederländerna, 2263
        • Haaglanden Medisch Centrum
  • Schweiz
      • Bern, Schweiz, 3010
        • Inselspital Bern
      • Lausanne, Schweiz, 1011
        • Centre Hospitalier Universitaire Vaudois (CHUV)
  • Spanien
      • Barcelona, Spanien, 08036
        • Hospital Clinic de Barcelona
      • Barcelona, Spanien, 08035
        • Vall d'Hebron Institute of Oncology (VHIO)
      • Madrid, Spanien
        • Hospital Universitario 12 de Octubre
      • Madrid, Spanien, 28050
        • Hospital Universitario HM Sanchinarro
      • Seville, Spanien, 41013
        • Hospital Universitario Virgen del Rocío
  • Sverige
      • Gothenburg, Sverige, 413 45
        • Sahlgrenska University Hospital
      • Uppsala, Sverige, 75185
        • Akademiska sjukhuset
  • Tyskland
      • Berlin, Tyskland, 10117
        • Charité Universitätsmedizin Berlin
      • Chemnitz, Tyskland, 09113
        • Klinikum Chemnitz gGmbH
      • Cologne, Tyskland
        • Neurochirurgie uniklinik Köln
      • Dresden, Tyskland, 01307
        • Universitätsklinikum Carl Gustav Carus Dresden
      • Essen, Tyskland, 45147
        • Universitätsklinikum Essen Klinik für Neurologie
      • Münster, Tyskland, 48149
        • University Hospital Munster
  • Österrike
      • Innsbruck, Österrike, 6020
        • Medizinische Universitaet Innsbruck

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 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.
Enhet: SonoCloud-9 (SC9)

Implantation of SC9 device and repeat activation at constant acoustic pressure

Läkemedel: Carboplatin

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].

Andra namn:
  • Cyklobutandikarboxylsyra (CBDCA)
Aktiv komparator: 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.
Läkemedel: Lomustine

Dosed and administered per labelling.

Andra namn:
  • 1-(2-kloretyl)-3-cyklohexyl-1-nitrosourea (CCNU)
Läkemedel: Temozolomide

Dosed and administered per labelling.

Andra namn:
  • Temodal

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Overall survival (OS)
Tidsram: Up to 24 months

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).
Up to 24 months

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Tumor Growth Rate
Tidsram: Up to week 24

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).
Up to week 24
Progression Free Survival (PFS)
Tidsram: Up to 24 months

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.
Up to 24 months
Overall survival at 12 months (OS12)
Tidsram: 12 months

Defined as the proportion of participants alive at 12 months
12 months
Overall survival at 18 months (OS18)
Tidsram: 18 months

Defined as the proportion of participants alive at 18 months
18 months
Progression-free survival at 6 months (PFS6)
Tidsram: 6 months

Defined as the proportion of participants without disease progression or death due to any cause at 6 months.
6 months

Andra resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Safety and Tolerability
Tidsram: Up to week 24

Frequency and severity of adverse events scored according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, from surgery to End-of-Trial Intervention visit
Up to week 24

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

CarThera

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Användbara länkar

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

29 januari 2024

Primärt slutförande (Beräknad)

28 januari 2028

Avslutad studie (Beräknad)

30 juni 2028

Studieregistreringsdatum

Först inskickad

5 juni 2023

Först inskickad som uppfyllde QC-kriterierna

5 juni 2023

Första postat (Faktisk)

13 juni 2023

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

5 november 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

4 november 2026

Senast verifierad

1 augusti 2026

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • SC9-GBM-03
  • 2023-505829-14-00 (Annan identifierare: EU CT Number)
  • 2023 (U.S.S. NIH-anslag/kontrakt)

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

NEJ

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Ja

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

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