Adebrelimab Plus Temozolomide ± Hyperbaric Oxygen for Primary Glioblastoma

Korábbi kezelés

• Prior anti-angiogenic, targeted, immunotherapy (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, CTLA-4 antibody etc.).
• Prior interstitial brachytherapy, implanted chemotherapy, local injection, convection-enhanced delivery; prior Gliadel wafer placement; prior Optune device usage.
• Dexamethasone >4 mg/day at adjuvant treatment initiation.
• History of immunodeficiency, or receiving immunosuppressive agents within 7 days before first study drug (except dexamethasone ≤4 mg daily).
• Uncontrolled concurrent severe disease: active infection, symptomatic congestive heart failure, unstable angina, arrhythmia, uncontrolled hypertension or psychiatric condition interfering with study compliance.
• Severe anemia or concomitant medications interfering temozolomide absorption.
• Participated in other relevant clinical trials within prior 3 months.
• Immunodeficiency including active hepatitis; HBV-DNA ≥1000 IU/ml; HCV-RNA ≥1000 IU/ml. Chronic HBV carrier with HBV-DNA<2000 IU/ml must receive concurrent antiviral treatment to be eligible.

Más betegség

• Progressive disease according to iRANO criteria. Suspicious pseudo-progression should be further evaluated by advanced imaging.
• Known hypersensitivity to temozolomide or adebrelimab components.
• Active systemic autoimmune disease requiring systemic therapy within past 2 years; physiological replacement therapy (thyroxine, insulin etc.) are allowed.
• Medical conditions unsuitable for hyperbaric oxygen therapy or immunotherapy.
• Uncontrolled major psychiatric disorder including depression with CESD-R score ≥16.
• Cognitive impairment preventing neuro-oncology assessment.
• Other malignant tumor within past 5 years (except cured carcinoma in-situ, basal-cell skin carcinoma). Poor compliance unable to follow protocol.
• Substance-use disorder (DSM-V criteria: alcohol or drug addiction).
• Active infection or unexplained fever>38.5℃ at screening / before first dosing (fever attributed to tumor is permitted).

Laborértékek

• Active cardiac disease within 6 months prior to screening: myocardial infarction, unstable angina; LVEF<50%, poorly controlled arrhythmia.

Egyéb

• Multifocal glioblastoma (separate tumor lesions without overlapping T2/FLAIR signal), or leptomeningeal metastasis.
• Tumor completely located in infratentorial region.
• Pregnant or lactating women.
• Life-threatening complication or vegetative state after chemoradiotherapy.
• Investigator's judgment that subject is inappropriate for this trial.

• Age 18-70 years, male or female.
• Newly-diagnosed primary glioblastoma histologically-confirmed; received maximal safe resection or biopsy, and completed standard concurrent chemoradiotherapy with temozolomide.
• Dexamethasone dose ≤4 mg/day at initiation of adjuvant study treatment.
• Karnofsky Performance Status(KPS) ≥70.
• Expected survival ≥3 months.
• Adequate bone marrow: ANC ≥1.5×10\^9/L; Hb ≥90 g/dL; PLT ≥100×10\^9/L; WBC ≥3.0×10\^9/L.
• Adequate liver function: ALT/AST/ALP ≤2.5×ULN (≤5×ULN if liver metastasis); total bilirubin <1.5×ULN.
• Adequate coagulation function: PT, APTT, INR ≤1.5×ULN.
• Female not pregnant / lactating; effective contraception required for fertile females and males during study and 6-month after last study treatment.
• Signed written informed consent, willing to comply with study procedures.
• Not participating in other interventional clinical trials.