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JOURNAL ONKOLOGIE – STUDIE
SONOBIRD

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

Rekrutierend

NCT-Nummer:
NCT05902169

Studienbeginn:
Januar 2024

Letztes Update:
24.04.2024

Wirkstoff:
Carboplatin, Lomustine, Temozolomide

Indikation (Clinical Trials):
Glioblastoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
CarThera

Collaborator:
-

Kontakt

Studienlocations
(3 von 13)

Hôpital Neurologique Pierre Wertheimer
Bron
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Studien-Informationen

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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

1. Overall survival (OS) (Time Frame - Up to 24 months):
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).



Secondary outcome:

1. Tumor Growth Rate (Time Frame - Up to week 24):
Tumor Growth Rate will be determined by measuring hyperintense tumor volume using T1w contrast-enhancing tumor-related region from post-surgery MRI baseline to unequivocal progression MRI (i.e., suspected radiologic progression confirmed by repeat scan).

2. Progression Free Survival (PFS) (Time Frame - Up to 24 months):
Defined as the time from date of randomization to the earlier of the following events: unequivocal tumor progression as determined by IRC per RANO criteria or death due to any cause.

3. Overall survival at 12 months (OS12) (Time Frame - 12 months):
Defined as the proportion of participants alive at 12 months

4. Overall survival at 18 months (OS18) (Time Frame - 18 months):
Defined as the proportion of participants alive at 18 months

5. Progression-free survival at 6 months (PFS6) (Time Frame - 6 months):
Defined as the proportion of participants without disease progression or death due to any cause at 6 months.

Studien-Arme

  • 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.

Geprüfte Regime

  • SonoCloud-9 (SC9):
    Implantation of SC9 device and repeat activation at constant acoustic pressure
  • Carboplatin (CycloButane DiCarboxylic Acid (CBDCA)):
    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].
  • Lomustine (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)):
    Dosed and administered per labelling.
  • Temozolomide (Temodal):
    Dosed and administered per labelling.

Quelle: ClinicalTrials.gov


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