Feasibility Assessment of a Medical Device for Tumour Cell Retention and Radiotherapy Sensitization in Patients With Suspected High-grade Glioma

This clinical investigation is designed to evaluate the safety of the GlioHook implant, as measured by the occurrence of adverse events related to the GlioHook implant, as well as events involving the need for device removal, in patients with high-grade glioma undergoing surgical resection followed by standard of care. Preliminary efficacy of the medical device such as Progression-Free Survival (PFS) will also be assessed.

• GlioHook device (Device), also known as GlioHook: GlioHook is a sterile medical device designed to be implanted after tumour resection surgery in suspected high grade glioma patients, covering the entire surface of the tumour resection margins.

Primary outcomes

• To evaluate the safety of the GlioHook implant, as measured by the occurrence of adverse events related to the GlioHook implant, as well as events involving the need for device removal [24 months]: Incidence of adverse events directly related to the implant of the device during follow-up, measured following NCI-CTCAE v6.0 guidelines, including events that involve the need of device removal.

Secondary outcomes

• To evaluate the preliminary efficacy of GlioHook, measured as Progression-Free Survival (PFS), defined according to RANO 2.0 criteria. [24 months]: PFS will be defined as the time from the date of surgery to the date of first documented disease progression or death from any cause, whichever occurs first.
• 6 months Progression-Free Survival (PFS) [6 months]: The 6-month PFS rate will also be reported. PFS will be defined as the time from the date of surgery to the date of first documented disease progression or death from any cause, whichever occurs first.
• Adjuvant Progression-Free Survival (PFS) [24 months.]: PFS will be also analyzed from start of adjuvant treatment. PFS will be defined as the time from the start of adjuvant treatment to the date of first documented disease progression or death from any cause, whichever occurs first.
• To evaluate the preliminary efficacy of GlioHook, measured as Overall Survival (OS). [24 months]: Overall Survival (OS). OS will be defined as time from date of surgery to date of death from any cause. OS will be also analyzed from start of adjuvant treatment.
• To evaluate changes in quality of life during the follow-up period (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)) [6 months]: Percentage of patients maintaining stable or improved quality of life during the first 6 months of follow-up, compared with baseline.
• To evaluate changes in quality of life during the follow-up period (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Brain Cancer Module (EORTC QLQ-BN20)) [6 months]: Percentage of patients maintaining stable or improved quality of life during the first 6 months of follow-up, compared with baseline.
• To evaluate changes in neurological function during the follow-up period (Neurologic Assessment in Neuro-Oncology (NANO scale)) [6 months]: Percentage of patients maintaining stable or improved neurological function during the first 6 months of follow-up, compared with baseline.

Sex: All, ages: 18 Years to 70 Years

Inclusion Criteria:

1. Willing and able to provide written informed consent prior to the performance of any study-specific procedures.
2. Age ≥18 and <70 years at the time of consent.
3. Suspected newly diagnosed unifocal high-grade glioma, as suggested by preoperative MRI imaging.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
5. Supratentorial and/or lobar tumor mass with a volume of less than 60cm3 as assessed by preoperative MRI.
6. Patient scheduled to undergo surgical resection of the target brain lesion, with an expected extent of resection (EOR) ≥90% based on preoperative imaging and surgical planning and according to the investigator's criteria. The anticipated EOR should be verified intraoperatively using a validated available method depending on availability at study site, such as 5-aminolevulinic acid (5-ALA) fluorescence guidance, ultrasound, or MRI.
7. Candidate to receive standard-of-care treatment for newly diagnosed glioblastoma, according to current clinical practice and the investigator's judgment.
8. Able to undergo contrast-enhanced MRI.
9. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and study procedures and accessible for follow-up after completion of study treatment.
10. For women of childbearing potential (WOCBP):

    * Must have a negative serum or urine pregnancy test within 7 days prior to inclusion.
    * Must not be pregnant or breastfeeding at the time of inclusion.
    * Must agree to use a highly effective method of contraception during the entire study participation period and for at least 6 months after the last dose of temozolomide.
11. Male and female patients of reproductive potential must agree to use highly effective contraceptive methods.

Exclusion Criteria:

1. Life expectancy <3 months, as estimated by the investigator.
2. Surgical resection cannot be assured or is considered not feasible or unsafe based on preoperative assessment.
3. Tumor located in the posterior fossa or involving critical subcortical structures (e.g., midbrain, brainstem, ventricles, or basal ganglia), where safe surgical resection cannot be achieved.
4. Presence of multifocal, bilateral, or recurrent tumor, or prior diagnosis of glioblastoma or other intracranial malignancy.
5. Extent of tumor resection <90%. The EOR should be verified intraoperatively using a validated available method depending on availability at study site, such as 5-aminolevulinic acid (5-ALA) fluorescence guidance, ultrasound, or MRI. However, it is up to the neurosurgeon to assess, after reviewing the available data and the resection itself, whether the patient meets the criteria for implantation.
6. Significant active or uncontrolled concurrent medical conditions, including but not limited to:

   * Active infection requiring systemic therapy,
   * Symptomatic congestive heart failure,
   * Unstable angina pectoris,
   * Clinically significant cardiac arrhythmia,
   * Uncontrolled hypertension,
   * Severe pulmonary, hepatic, or renal disease,
   * Psychiatric or social conditions that, in the opinion of the investigator, would interfere with study compliance or follow-up.
   * Severe blood clotting disorders
7. Known hypersensitivity to bovine-derived collagen or other components of the medical device.
8. Contraindication to contrast-enhanced MRI, including known allergy to gadolinium or presence of non-MRI-compatible implants.
9. Contraindication to receive radiotherapy or temozolomide, including prior cranial irradiation exceeding safe cumulative dose limits.
10. Participation in another interventional clinical trial or use of an investigational product within 30 days prior to inclusion, or planned participation during this clinical investigation.
11. Women who are pregnant or breastfeeding.
12. Men or women of reproductive potential unwilling to use adequate contraception, as defined in the inclusion criteria.
13. Inability or unwillingness to comply with clinical investigation procedures, follow-up schedule, or CIP requirements, as judged by the investigator.