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

NCT05902169 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: SC9-GBM-032023-505829-14-00
• Study Type: interventional
• Target: 560
• Locations: 10 countries
• Sites: 48

Brief 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.

Conditions

Glioblastoma; Recurrent Glioblastoma; GBM

Keywords

carboplatin; SonoCloud; blood-brain barrier; Low Intensity Pulsed Ultrasound (LIPU)

Outcome Measures

Primary Outcomes (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).

  Up to 24 months

Secondary Outcomes (5)

• Tumor Growth Rate

  Up to week 24

• Progression Free Survival (PFS)

  Up to 24 months

• Overall survival at 12 months (OS12)

  12 months

• Overall survival at 18 months (OS18)

  18 months

• Progression-free survival at 6 months (PFS6)

  6 months

Other Outcomes (1)

• Safety and Tolerability

  Up to week 24

Study Arms (2)

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.

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.

Drug: Lomustine; Drug: Temozolomide

Interventions

SonoCloud-9 (SC9) DEVICE

Implantation of SC9 device and repeat activation at constant acoustic pressure

Experimental Arm: SonoCloud-9 Ultrasound + Carboplatin

Carboplatin DRUG

Dose of carboplatin AUC 5 mg/ml.min-1 calculated using Calvert's formula: Dose (mg) = target AUC (mg/mL x minute) x \[glomerular filtration rate (GFR) mL/minute + 25\].

Also known as: CycloButane DiCarboxylic Acid (CBDCA)

Experimental Arm: SonoCloud-9 Ultrasound + Carboplatin

Lomustine DRUG

Dosed and administered per labelling.

Also known as: 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)

Control Arm: SoC single agent chemotherapy TMZ or CCNU

Temozolomide DRUG

Dosed and administered per labelling.

Also known as: Temodal

Control Arm: SoC single agent chemotherapy TMZ or CCNU

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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 candidate for craniotomy and at least 50% resection of enhancing region
• 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

Sponsors & Collaborators

• CarThera: lead

Study Sites (48)

Mayo Clinic Arizona

Phoenix, Arizona, 805054, United States

ACTIVE NOT RECRUITING

University of California, San Francisco

San Francisco, California, 94143, United States

ACTIVE NOT RECRUITING

UCHealth

Aurora, Colorado, 80011, United States

ACTIVE NOT RECRUITING

Mayo Clinic of Jacksonville Florida

Jacksonville, Florida, 32224, United States

ACTIVE NOT RECRUITING

Miami Cancer Institute

Miami, Florida, 33176, United States

ACTIVE NOT RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

ACTIVE NOT RECRUITING

Winship Cancer Institute at Emory University

Atlanta, Georgia, 30322, United States

ACTIVE NOT RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

ACTIVE NOT RECRUITING

Indiana University Health

Indianapolis, Indiana, 46202, United States

ACTIVE NOT RECRUITING

John Hopkins University

Baltimore, Maryland, 21287, United States

ACTIVE NOT RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

ACTIVE NOT RECRUITING

Weill Cornell Medicine

New York, New York, 10021, United States

ACTIVE NOT RECRUITING

NewYork-Presbyterian / Columbia University Irving Medical Center

New York, New York, 10032, United States

ACTIVE NOT RECRUITING

Lennox Hill Hospital

New York, New York, 10075, United States

ACTIVE NOT RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27516, United States

ACTIVE NOT RECRUITING

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

ACTIVE NOT RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

ACTIVE NOT RECRUITING

University of Texas Houston Health Science Center

Houston, Texas, 77030, United States

ACTIVE NOT RECRUITING

University of Utah, Hunstman Cancer Institute

Salt Lake City, Utah, 84112, United States

ACTIVE NOT RECRUITING

Medizinische Universitaet Innsbruck

Innsbruck, 6020, Austria

ACTIVE NOT RECRUITING

Universitair Ziekenhuis Brussel

Brussels, Belgium

RECRUITING

Universitair Ziekenhuis Leuven

Leuven, Belgium

ACTIVE NOT RECRUITING

CHU de Liège

Liège, Belgium

RECRUITING

Rigshospitalet

Copenhagen, 2100, Denmark

ACTIVE NOT RECRUITING

Odense University Hospital

Odense, 5000, Denmark

ACTIVE NOT RECRUITING

Hôpital Neurologique Pierre Wertheimer

Bron, France

RECRUITING

Hôpital de La Timone

Marseille, France

RECRUITING

Hôpital de la Pitié-Salpêtrière

Paris, France

RECRUITING

Hôpital Foch

Suresnes, 92150, France

ACTIVE NOT RECRUITING

Charité Universitätsmedizin Berlin

Berlin, 10117, Germany

ACTIVE NOT RECRUITING

Klinikum Chemnitz gGmbH

Chemnitz, 09113, Germany

ACTIVE NOT RECRUITING

Neurochirurgie uniklinik Köln

Cologne, Germany

ACTIVE NOT RECRUITING

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, 01307, Germany

ACTIVE NOT RECRUITING

Universitätsklinikum Essen Klinik für Neurologie

Essen, 45147, Germany

ACTIVE NOT RECRUITING

Ospedale Bellaria

Bologna, 40139, Italy

ACTIVE NOT RECRUITING

Ospedale Civile di Livorno

Livorno, 57124, Italy

ACTIVE NOT RECRUITING

Istituto Oncologico Veneto

Padua, Italy

ACTIVE NOT RECRUITING

Irccs Istituto Clinico Humanitas

Rozzano, 20089, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino

Torino, 10126, Italy

ACTIVE NOT RECRUITING

Erasmus Medisch Centrum (Erasmus MC)

Rotterdam, Netherlands

ACTIVE NOT RECRUITING

Haaglanden Medisch Centrum

The Hague, 2263, Netherlands

ACTIVE NOT RECRUITING

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, 08035, Spain

ACTIVE NOT RECRUITING

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

ACTIVE NOT RECRUITING

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

ACTIVE NOT RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Spain

RECRUITING

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

ACTIVE NOT RECRUITING

Inselspital Bern

Bern, 3010, Switzerland

ACTIVE NOT RECRUITING

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, 1011, Switzerland

ACTIVE NOT RECRUITING

Related Publications (2)

• 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.

  PMID: 27306666 BACKGROUND

• Sonabend 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.

  PMID: 37142373 BACKGROUND

Related Links

• CARTHERA

MeSH Terms

Conditions

Glioblastoma

Interventions

Carboplatin; Lomustine; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Carole Desseaux

CONTACT

+33 472 626 268; contact@carthera.eu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2023
• First Posted: June 13, 2023
• Study Start: January 29, 2024
• Primary Completion (Estimated): January 28, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: June 5, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (19); ES (5); DE (5); FR (4); CH (2); DK (2); BE (3); AU (1); IT (5); NL (2)