Levetiracetam Extended-Release Plus Stupp Protocol for Hypoxic IDH-Wildtype Glioblastoma (ELITE)

Inclusion Criteria:

• Age ≥18 and <70 years. Histopathologically confirmed primary IDH-wildtype glioblastoma (WHO CNS Grade 4, 2021 WHO Classification).

Tumor with hypoxic features confirmed by immunohistochemistry (HIF-1α and CA9 expression score ≥2).

Planned to receive standard Stupp protocol after maximal safe surgical resection.

Karnofsky Performance Status (KPS) ≥70.

Adequate bone marrow function:

Hemoglobin ≥90 g/L Platelet count ≥100 × 10⁹/L White blood cell count ≥3.0 × 10⁹/L Absolute neutrophil count ≥1.5 × 10⁹/L

Adequate hepatic function:

AST and ALT ≤2.5 × upper limit of normal (ULN) Total bilirubin <50 μmol/L.

Adequate renal function:

Serum creatinine ≤1.5 × ULN Creatinine clearance (CrCl) ≥36 mL/min. No previous chemotherapy, radiotherapy, immunotherapy, or targeted therapy for glioblastoma.

No history of epilepsy or prior antiepileptic drug treatment. Ability to understand the study procedures and provide written informed consent.

Willing and able to comply with study procedures and follow-up.

Exclusion Criteria:

• Known hypersensitivity to levetiracetam, pyrrolidone derivatives, or any study drug component.

History of epilepsy or previous treatment with antiepileptic drugs. Requirement for concomitant use of other antiepileptic drugs during the study. Presence of another active malignancy. Severe cardiac, hepatic, renal, hematologic, or other uncontrolled systemic diseases.

Uncontrolled metabolic disorders or severe infections. Active hepatitis B, hepatitis C, HIV infection, active syphilis, or active tuberculosis.

Participation in another interventional clinical trial within 4 weeks before screening.

History of organ transplantation or hematopoietic stem cell transplantation. Pregnancy or breastfeeding, or plans for pregnancy during the study period. Psychiatric illness, cognitive impairment, or poor compliance that would interfere with study participation.

Any other condition that, in the investigator's judgment, would make participation unsafe or interfere with study evaluation.