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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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 (

- 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) 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05902169
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	CarThera
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Belgium, France, Germany, Italy, Netherlands, Spain, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Glioblastoma, Recurrent Glioblastoma, GBM
Study Website:	View Trial Website

Arms & Interventions

Arms

Experimental: 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.

Active Comparator: 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.

Interventions

Device: - SonoCloud-9 (SC9)

Implantation of SC9 device and repeat activation at constant acoustic pressure

Drug: - 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].

Drug: - Lomustine

Dosed and administered per labelling.

Drug: - Temozolomide

Dosed and administered per labelling.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Northwestern University, Chicago, Illinois

Status

Not yet recruiting

Address

Northwestern University

Chicago, Illinois, 60611

Site Contact

Rimas Lukas, MD

carole.desseaux@carthera.eu

+33 472 626 268

New York, New York

Status