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Sonocloud-9 i forbindelse med Carboplatin Versus Standard-of-Care kjemoterapier (CCNU eller TMZ) ved tilbakevendende GBM (SONOBIRD)

4. november 2026 oppdatert av: CarThera

En randomisert, åpen, multisentrisk, to-arms pivotal studie av SonoCloud-9 kombinert med Carboplatin (CBDCA) vs Standard of Care Lomustine (CCNU) eller Temozolomide (TMZ) hos pasienter som gjennomgår planlagt reseksjon for første tilbakefall 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.

Studieoversikt

Status

Aktiv, ikke rekrutterende

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Antatt)

560

Fase

  • Fase 3

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Belgia
      • Brussels, Belgia
        • Universitair Ziekenhuis Brussel
      • Leuven, Belgia
        • Universitair Ziekenhuis Leuven
      • Liège, Belgia
        • CHU de Liège
  • Danmark
      • Copenhagen, Danmark, 2100
        • Rigshospitalet
      • Odense, Danmark, 5000
        • Odense University Hospital
  • Forente stater
    • Arizona
      • Phoenix, Arizona, Forente stater, 805054
        • Mayo Clinic Arizona
    • California
      • Los Angeles, California, Forente stater, 90095
        • UCLA
      • Los Angeles, California, Forente stater, 90027
        • Kaiser Permanente
      • San Francisco, California, Forente stater, 94143
        • University of California, San Francisco
      • San Francisco, California, Forente stater, 94109
        • Sutter Health - California Pacific Medical Center
    • Colorado
      • Aurora, Colorado, Forente stater, 80011
        • UCHealth
    • Florida
      • Jacksonville, Florida, Forente stater, 32224
        • Mayo Clinic of Jacksonville Florida
      • Miami, Florida, Forente stater, 33176
        • Miami Cancer Institute
      • Tampa, Florida, Forente stater, 33612
        • Moffitt Cancer Center
    • Georgia
      • Atlanta, Georgia, Forente stater, 30322
        • Winship Cancer Institute at Emory University
    • Illinois
      • Chicago, Illinois, Forente stater, 60611
        • Northwestern University
    • Indiana
      • Indianapolis, Indiana, Forente stater, 46202
        • Indiana University Health
    • Maryland
      • Baltimore, Maryland, Forente stater, 21287
        • John Hopkins University
    • Minnesota
      • Rochester, Minnesota, Forente stater, 55905
        • Mayo Clinic Rochester
    • New York
      • New York, New York, Forente stater, 10021
        • Weill Cornell Medicine
      • New York, New York, Forente stater, 10075
        • Lennox Hill Hospital
      • New York, New York, Forente stater, 10032
        • NewYork-Presbyterian / Columbia University Irving Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, Forente stater, 27516
        • University of North Carolina
    • Ohio
      • Cleveland, Ohio, Forente stater, 44106
        • Neurological Institute Brain Tumor Centre Taussig Cancer Cente
    • Pennsylvania
      • Hershey, Pennsylvania, Forente stater, 17033
        • Penn State Health Milton S. Hershey Medical Center
    • Texas
      • Dallas, Texas, Forente stater, 75390
        • University of Texas Southwestern Medical Center
      • Houston, Texas, Forente stater, 77030
        • University of Texas Houston Health Science Center
    • Utah
      • Salt Lake City, Utah, Forente stater, 84112
        • University of Utah, Hunstman Cancer Institute
  • 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
  • Italia
      • Bologna, Italia, 40139
        • Ospedale Bellaria
      • Livorno, Italia, 57124
        • Ospedale Civile di Livorno
      • Padua, Italia
        • Istituto Oncologico Veneto
      • Roma, Italia
        • IFO - Istituto Nazionale Tumori Regina Elena
      • Rozzano, Italia, 20089
        • Irccs Istituto Clinico Humanitas
      • Torino, Italia, 10126
        • Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino
  • Nederland
      • Rotterdam, Nederland
        • Erasmus Medisch Centrum (Erasmus MC)
      • The Hague, Nederland, 2263
        • Haaglanden Medisch Centrum
  • Spania
      • Barcelona, Spania, 08036
        • Hospital Clinic de Barcelona
      • Barcelona, Spania, 08035
        • Vall d'Hebron Institute of Oncology (VHIO)
      • Madrid, Spania
        • Hospital Universitario 12 de Octubre
      • Madrid, Spania, 28050
        • Hospital Universitario HM Sanchinarro
      • Seville, Spania, 41013
        • Hospital Universitario Virgen del Rocío
  • Sveits
      • Bern, Sveits, 3010
        • Inselspital Bern
      • Lausanne, Sveits, 1011
        • Centre Hospitalier Universitaire Vaudois (CHUV)
  • 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
  • Østerrike
      • Innsbruck, Østerrike, 6020
        • Medizinische Universitaet Innsbruck

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 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

Legemiddel: 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].

Andre navn:
  • Syklobutan dikarboksylsyre (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.
Legemiddel: Lomustine

Dosed and administered per labelling.

Andre navn:
  • 1-(2-kloretyl)-3-cykloheksyl-1-nitrosourea (CCNU)
Legemiddel: Temozolomide

Dosed and administered per labelling.

Andre navn:
  • Temodal

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Overall survival (OS)
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Tumor Growth Rate
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 12 months

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

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

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

Andre resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Safety and Tolerability
Tidsramme: 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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

CarThera

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Hjelpsomme linker

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

29. januar 2024

Primær fullføring (Antatt)

28. januar 2028

Studiet fullført (Antatt)

30. juni 2028

Datoer for studieregistrering

Først innsendt

5. juni 2023

Først innsendt som oppfylte QC-kriteriene

5. juni 2023

Først lagt ut (Faktiske)

13. juni 2023

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

5. november 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

4. november 2026

Sist bekreftet

1. august 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • SC9-GBM-03
  • 2023-505829-14-00 (Annen identifikator: EU CT Number)
  • 2023 (U.S. NIH-stipend/kontrakt)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Abonnere