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

Phase 2Not Yet RecruitingNCT07758062

Tianjin Medical University General Hospital140 enrolled

Overview

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and is associated with poor prognosis despite standard treatment with maximal safe resection followed by radiotherapy plus temozolomide (the Stupp regimen). Tumor hypoxia is associated with treatment resistance and poor clinical outcomes. This multicenter, prospective, controlled study aims to evaluate whether levetiracetam extended-release combined with the Stupp regimen improves progression-free survival and overall survival in patients with hypoxic IDH-wildtype glioblastoma while maintaining an acceptable safety profile. Eligible patients with newly diagnosed hypoxic IDH-wildtype glioblastoma will receive either levetiracetam extended-release plus the Stupp regimen or the standard Stupp regimen. Clinical efficacy, safety, and quality-of-life outcomes will be evaluated during follow-up.

Glioblastoma remains one of the most aggressive primary brain tumors, with limited survival despite current standard treatment. Increasing evidence suggests that tumor hypoxia contributes to therapeutic resistance and poor prognosis. Levetiracetam has demonstrated potential antitumor activity in addition to its established role as an antiepileptic agent and may enhance the efficacy of temozolomide in patients with glioblastoma. This is a multicenter, prospective, open-label, controlled investigator-initiated study designed to evaluate the efficacy and safety of levetiracetam extended-release combined with the Stupp regimen in patients with newly diagnosed hypoxic IDH-wildtype glioblastoma. Approximately 140 eligible participants will be enrolled from multiple centers in China. Participants will receive either levetiracetam extended-release combined with the standard Stupp regimen or the standard Stupp regimen alone according to the study protocol. The primary endpoint is progression-free survival. Secondary endpoints include overall survival, objective response rate, disease control rate, safety, quality of life, and exploratory biomarker analyses. Participants will be followed according to the protocol until completion of the study. The study is expected to provide clinical evidence regarding whether levetiracetam extended-release can improve outcomes in patients with hypoxic IDH-wildtype glioblastoma without compromising safety.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Eligibility

Sex: ALLMin age: 18 YearsMax age: 69 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Progression-Free Survival (PFS)

Progression-free survival, defined as the time from study enrollment to disease progression or death from any cause, whichever occurs first.

Time frame: Up to 24 months

Secondary Outcomes

Overall Survival (OS)

Overall survival, defined as the time from study enrollment to death from any cause.

Time frame: Up to 36 months

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts