Clinical Trial 22563

• Overview

  Study Title:

  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

  Objective:

  Primary Objectives: To evaluate and compare the survival outcome of patients with first recurrence of glioblastoma undergoing surgical debulking/resection followed by either implantation of the SC9 device and repeat BBB opening in association with carboplatin chemotherapy or standard of care 2nd line chemotherapy with either lomustine or temozolomide (per best physician s choice and best practice). Secondary Objectives: To evaluate and compare the clinical efficacy (regarding Progression Free Survival) To evaluate and compare the safety To evaluate and compare the clinical efficacy (regarding Tumor Growth Rate) To evaluate and compare patient reported outcome with regards to quality of life.

• Treatments

  Therapies:

  Chemotherapy (NOS)

  Medications:

  Lomustine (CeeNU); Paraplatin (carboplatin); Temodal (Temozolomide); Temozolomide (); carboplatin ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Histologically proven glioblastoma (WHO criteria 2021), absence of IDH mutation demonstrated by negative IDH1 R132H staining on IHC.
  • 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> First, unequivocal disease progression with: 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, 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.
  • 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).
  • WHO performance status ≤ 2 (equivalent to Karnofsky Performance Status, KPS ≥ 70).
  • Age ≥ 18 years.
  • Participant must be recovered from acute toxic effects (> Adequate hematologic, hepatic, and renal laboratory values within 14 days of inclusion.
  • Patient able to understand clinical trial information and willing to provide signed and informed consent.
  • 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.
  • 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.
  • 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)
  • Other inclusion criteria may apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Multifocal enhancing tumor on T1w (unless all localized in a 5 cm diameter area)
  • Posterior fossa tumor
  • Known BRAF/ NTKR mutated patients
  • 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)
  • 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.
  • Contra-indication to carboplatin, CCNU or TMZ
  • Known history of hypersensitivity reactions to perflutren lipid microsphere components or to any of the inactive ingredients in ultrasound resonator
  • Patient has received bevacizumab for other reasons (such as tumor progression) than treating edema
  • Peripheral neuropathy or neuropathy ≥ grade 2
  • Uncontrolled epilepsy or evidence of intracranial pressure
  • Patient with known intracranial aneurism or having presented intra-tumor significant spontaneous hemorrhage
  • Patient with unremovable coils, clips, shunts, intravascular stents, and/or wafer, or reservoirs
  • 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.
  • Patient receiving enzyme-inducing antiepileptic drugs (namely phenytoin, carbamazepine and derivatives, phenobarbital), unless switched on another antiepileptic regimen
  • 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
  • Patient with known or suspected active or chronic infections
  • 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
  • Known sensitivity/allergy to gadolinium, or other intravascular contrast agents
  • Patient with impaired thermo-regulation or temperature sensation
  • Pregnant, or breastfeeding patient
  • 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
  • Patients under guardianship, curatorship, under legal protection or deprived of liberty by an administrative or judicial decision
  • Other exclusion criteria may apply

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