Silibinin in Association With Concomitant Chemoradiotherapy and Maintenance Temozolomide in STAT3 Positive IDH Wild-type, Newly Diagnosed Glioblastoma Patients

Multicenter, double-blind, placebo-controlled, randomized trial. Patients affected by STAT3 positive newly diagnosed glioblastoma will be eligible. Patients are randomized using a stratified block randomization method with a 1:1 ratio in two arms: • Experimental/Control arm: Concomitant radiotherapy (60 gy in 30 fractions) + temozolomide 75mg/mq + silibinin/placebo 2 sachets/day dissolved in water throughout concomitant treatment followed by temozolomide cp, 150 mg/m2-200mg/m2, g1-5 q28d + silibinin/placebo 2 sachets/day dissolved in water, day 1-28, q28d for 6-12 cycles. Silibinin/Placebo may be continued until disease progression at the discretion of the physician. Patients will be stratified based on: * Type of surgery (complete Vs partial) * MGMT methylation status (methylated Vs non-methylated) * ECOG PS (0-1 Vs 2)

Inclusion Criteria: * New histologically confirmed diagnosis of glioblastoma (WHO 2021) * Local availability of MGMT methylation status * Immunohistochemical positivity of activated STAT3 (pSTAT3) expression on the tumor tissue sample. STAT3 expression will be evaluated centrally by UOC Anatomia Patologica of Azienda Ospedale Università di Padova. * Chemoradiotherapy start within 7 weeks from surgery * Patients without disease progression after surgery * Availability of paraffin-embedded tumor tissue * Age ≥18 years * ECOG PS 0-2; Karnofsky 100-70 * Signing of informed consent prior to any study procedure * Patients (both males and females) should employ adequate contraceptive measures, which should be maintained during the whole duration of the trial (from screening to 6 months after the last dose of Temozolomide). * Have adequate bone marrow, liver and kidney function, as measured by the following laboratory assessments conducted within 10 days before the start of study treatment: * Hemoglobin \> 9.0 g/dl * Absolute neutrophil count (ANC) ≥1500/mm3 without granulocyte colony-stimulating factor (G-CSF) and other hematopoietic growth factors * Platelet count ≥100,000/μl * WBC ≥3.0 x 10 9 /L * Total bilirubin \