Silibinin in Association With Concomitant Chemoradiotherapy and Maintenance Temozolomide in STAT3 Positive IDH Wild-type, Newly Diagnosed Glioblastoma Patients: a Multicenter, Double-blind, Placebo-controlled, Randomized Study
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)
• 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 \<1.5 times the upper limit of normal
• ALT and AST \<3 x the upper limit of normal
• Serum creatinine \<1.5 times the upper limit of normal
• Glomerular filtration rate ≥ 30 mL/min/1.73 m2 according to the abbreviated formula Modified Diet in Renal Disease
• Alkaline phosphatase \<2.5 x ULN
• PT-INR/PTT \<1.5 x upper limit of normal (patients who are therapeutically anticoagulated with anticoagulant drugs will be able to participate provided there is no history of abnormal background in these parameters, based on history).
• Complete urinalysis
• Stable and decreasing corticosteroid dosage in the last 10 days before brain MRI