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

NCT ID: NCT05902169

Last Updated: 2025-11-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 560 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-29
• Study Completion Date: 2028-06-30

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)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

SonoCloud-9 (SC9)

Intervention Type: DEVICE

Implantation of SC9 device and repeat activation at constant acoustic pressure

Carboplatin

Intervention Type: 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].

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.

Group Type: ACTIVE_COMPARATOR

Lomustine

Intervention Type: DRUG

Dosed and administered per labelling.

Temozolomide

Intervention Type: DRUG

Dosed and administered per labelling.

Interventions

SonoCloud-9 (SC9)

Implantation of SC9 device and repeat activation at constant acoustic pressure

Intervention Type: DEVICE

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].

Intervention Type: DRUG

Lomustine

Dosed and administered per labelling.

Intervention Type: DRUG

Temozolomide

Dosed and administered per labelling.

Intervention Type: DRUG

Other Intervention Names

CycloButane DiCarboxylic Acid (CBDCA); 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU); Temodal

Eligibility 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 performed within 14 days of inclusion 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 candidate for craniotomy and at least 50% resection of enhancing region

5. 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)

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 of 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/1.73 m2 using Cockcroft Gault formula

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 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

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)

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CarThera

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Mayo Clinic Arizona

Phoenix, Arizona, United States

University of California, San Francisco

San Francisco, California, United States

UCHealth

Aurora, Colorado, United States

Mayo Clinic of Jacksonville Florida

Jacksonville, Florida, United States

Miami Cancer Institute

Miami, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Winship Cancer Institute at Emory University

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

Indiana University Health

Indianapolis, Indiana, United States

John Hopkins University

Baltimore, Maryland, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

Weill Cornell Medicine

New York, New York, United States

NewYork-Presbyterian / Columbia University Irving Medical Center

New York, New York, United States

Lennox Hill Hospital

New York, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

University of Texas Houston Health Science Center

Houston, Texas, United States

University of Utah, Hunstman Cancer Institute

Salt Lake City, Utah, United States

Medizinische Universitaet Innsbruck

Innsbruck, , Austria

Universitair Ziekenhuis Brussel

Brussels, , Belgium

Universitair Ziekenhuis Leuven

Leuven, , Belgium

CHU de Liège

Liège, , Belgium

Rigshospitalet

Copenhagen, , Denmark

Odense University Hospital

Odense, , Denmark

Hôpital Neurologique Pierre Wertheimer

Bron, , France

Hôpital de La Timone

Marseille, , France

Hôpital de la Pitié-Salpêtrière

Paris, , France

Hôpital Foch

Suresnes, , France

Charité Universitätsmedizin Berlin

Berlin, , Germany

Klinikum Chemnitz gGmbH

Chemnitz, , Germany

Neurochirurgie uniklinik Köln

Cologne, , Germany

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, , Germany

Universitätsklinikum Essen Klinik für Neurologie

Essen, , Germany

Ospedale Bellaria

Bologna, , Italy

Ospedale Civile di Livorno

Livorno, , Italy

Istituto Oncologico Veneto

Padua, , Italy

Irccs Istituto Clinico Humanitas

Rozzano, , Italy

Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino

Torino, , Italy

Erasmus Medisch Centrum (Erasmus MC)

Rotterdam, , Netherlands

Haaglanden Medisch Centrum

The Hague, , Netherlands

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitario HM Sanchinarro

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario Virgen del Rocío

Seville, , Spain

Inselspital Bern

Bern, , Switzerland

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, , Switzerland

Countries

United States; Austria; Belgium; Denmark; France; Germany; Italy; Netherlands; Spain; Switzerland

References

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.

Reference Type: BACKGROUND

PMID: 27306666 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 37142373 (View on PubMed)

Related Links

http://www.carthera.eu

CARTHERA

Other Identifiers

2023-505829-14-00

Identifier Type: OTHER

Identifier Source: secondary_id

SC9-GBM-03

Identifier Type: -

Identifier Source: org_study_id