Informations générales (source: ClinicalTrials.gov)
A Randomized, Open-label, Multicentric, Two-arm Pivotal Trial of SonoCloud-9 Combined With Carboplatin (CBDCA) vs Standard of Care Lomustine (CCNU) or Temozolomide (TMZ) in Patients Undergoing Planned Resection for First Recurrence Glioblastoma. (SONOBIRD)
Interventional
Phase 3
CarThera (Voir sur ClinicalTrials)
janvier 2024
juin 2028
29 avril 2025
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| HOPITAL FOCH | Nadia YOUNAN | 05/05/2025 07:12:14 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Hôpital de la Pitié-Salpêtrière - Paris - France | Ahmed Idbaih, MD | Contact (sur clinicalTrials) | |||
| Hôpital de La Timone - Marseille - France | Olivier Chinot, MD | Contact (sur clinicalTrials) | |||
| Hôpital Neurologique Pierre Wertheimer - Bron - France | François Ducray, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
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)
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.
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)
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.