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

Last updated: March 24, 2025
Sponsor: CarThera
Overall Status: Active - Recruiting

Phase

3

Condition

Gliomas

Astrocytoma

Treatment

Lomustine

SonoCloud-9 (SC9)

Carboplatin

Clinical Study ID

NCT05902169
SC9-GBM-03
2023-505829-14-00
  • Ages > 18
  • All Genders

Study 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. 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.

Eligibility Criteria

Inclusion

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:

  3. 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)

  4. One line of maintenance chemotherapy and/or immune- or biological therapy, (with or without Tumor-Treating Fields)

  5. First, unequivocal disease progression with

  6. measurable tumor (>100 mm2 or 1 cm3, based on RANO criteria) documented (e.g., increase of 25% in tumor diameter) on MRI performed within 14 days of inclusion and,

  7. 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

  8. Patient is candidate for craniotomy and at least 50% resection of enhancing region

  9. Maximal enhancing tumor diameter prior to inclusion ≤ 5 cm on T1w. (In case of planned lobectomy, post operative peritumoral brain or residual size ≤5 cm)

  10. WHO performance status ≤ 2 (equivalent to Karnofsky Performance Status (KPS) ≥ 70)

  11. Age ≥ 18 years

  12. 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:

  13. ≥ 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)

  1. ≥ 6 weeks of prior bevacizumab

  2. Adequate hematologic, hepatic, and renal laboratory values within 14 days of inclusion i.e.:

  3. Hemoglobin ≥ 10 g/dL, platelets ≥ 100,000/mm3, neutrophils ≥ 1500/mm3.

  4. Liver function test with ≤ grade 1 alterations, except if due to antiepileptic drug therapy or isolated increased bilirubin due to Gilbert syndrome

  5. Estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2 using Cockcroft Gault formula

  6. Patient able to understand clinical trial information and willing to provide signed and informed consent

  7. Patient of childbearing potential must have a negative pregnancy test within 14 days of 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

  8. 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.

  9. 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)

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, and/or previously infected surgical field, 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,...), 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.

Study Design

Total Participants: 560
Treatment Group(s): 4
Primary Treatment: Lomustine
Phase: 3
Study Start date:
January 29, 2024
Estimated Completion Date:
June 30, 2028

Connect with a study center

  • Universitair Ziekenhuis Brussel

    Brussel,
    Belgium

    Active - Recruiting

  • Universitair Ziekenhuis Leuven

    Leuven,
    Belgium

    Active - Recruiting

  • CHU de Liège

    Liège,
    Belgium

    Active - Recruiting

  • Hôpital Neurologique Pierre Wertheimer

    Bron,
    France

    Active - Recruiting

  • Hôpital de La Timone

    Marseille,
    France

    Active - Recruiting

  • Hôpital de la Pitié-Salpêtrière

    Paris,
    France

    Active - Recruiting

  • Hôpital Foch

    Suresnes, 92150
    France

    Active - Recruiting

  • Klinikum Chemnitz gGmbH

    Chemnitz, 09113
    Germany

    Active - Recruiting

  • Universitätsklinikum Carl Gustav Carus Dresden

    Dresden, 01307
    Germany

    Active - Recruiting

  • Universitätsklinikum Essen Klinik für Neurologie

    Essen, 45147
    Germany

    Active - Recruiting

  • Neurochirurgie uniklinik Köln

    Köln,
    Germany

    Active - Recruiting

  • Istituto Oncologico Veneto

    Padua,
    Italy

    Site Not Available

  • Erasmus Medisch Centrum (Erasmus MC)

    Rotterdam,
    Netherlands

    Active - Recruiting

  • Haaglanden Medisch Centrum

    The Hague, 2263
    Netherlands

    Active - Recruiting

  • Vall d'Hebron Institute of Oncology (VHIO)

    Barcelona, 08035
    Spain

    Active - Recruiting

  • Hospital Universitario 12 de Octubre

    Madrid,
    Spain

    Active - Recruiting

  • Hospital Universitario HM Sanchinarro

    Madrid, 28050
    Spain

    Active - Recruiting

  • Hospital Universitario Virgen del Rocío

    Sevilla, 41013
    Spain

    Active - Recruiting

  • Inselspital Bern

    Bern, 3010
    Switzerland

    Active - Recruiting

  • Centre Hospitalier Universitaire Vaudois (CHUV)

    Lausanne, 1011
    Switzerland

    Active - Recruiting

  • Mayo Clinic Arizona

    Phoenix, Arizona 805054
    United States

    Active - Recruiting

  • UCHealth

    Aurora, Colorado 80011
    United States

    Active - Recruiting

  • Mayo Clinic of Jacksonville Florida

    Jacksonville, Florida 32224
    United States

    Active - Recruiting

  • Miami Cancer Institute

    Miami, Florida 33176
    United States

    Active - Recruiting

  • Moffitt Cancer Center

    Tampa, Florida 33612
    United States

    Active - Recruiting

  • Northwestern University

    Chicago, Illinois 60611
    United States

    Active - Recruiting

  • Indiana University Health

    Indianapolis, Indiana 46202
    United States

    Active - Recruiting

  • John Hopkins University

    Baltimore, Maryland 21287
    United States

    Active - Recruiting

  • Mayo Clinic Rochester

    Rochester, Minnesota 55905
    United States

    Active - Recruiting

  • Lennox Hill Hospital

    New York, New York 10075
    United States

    Active - Recruiting

  • NewYork-Presbyterian / Columbia University Irving Medical Center

    New York, New York 10032
    United States

    Active - Recruiting

  • Weill Cornell Medicine

    New York, New York 10021
    United States

    Active - Recruiting

  • University of North Carolina

    Chapel Hill, North Carolina 27516
    United States

    Active - Recruiting

  • Penn State Health Milton S. Hershey Medical Center

    Hershey, Pennsylvania 17033
    United States

    Active - Recruiting

  • University of Texas Southwestern Medical Center

    Dallas, Texas 75390
    United States

    Active - Recruiting

  • University of Texas Houston Health Science Center

    Houston, Texas 77030
    United States

    Active - Recruiting

  • University of Utah, Hunstman Cancer Institute

    Salt Lake City, Utah 84112
    United States

    Active - Recruiting

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