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

Exclusion Criteria

• •Patients diagnosed with glioblastoma (WHO grade IV 2021) who have only had a diagnostic biopsy
• •Chemotherapy, immunotherapy, or antineoplastic therapy for glioblastoma
• •Negative immunohistochemistry of STAT3 expression on the tumor tissue sample
• •Diagnosis of another tumor or secondary brain localization
• •In the investigator's judgment, any evidence of severe or uncontrolled systemic disease including: uncontrolled hypertension; hemorrhagic diathesis; active infection with HBV, HCV, HIV. Screening for such chronic conditions is not required by the protocol; bone marrow reserve or organ dysfunction as demonstrated by laboratory tests.
• •Patients who are unable to comply with study procedures and requirements.
• •Contraindication to Brain MRI
• •Pregnant or breastfeeding patients
• •Patients who are unable to swallow capsules or sachets dissolved in water.
• •Patient unable to sign the Informed Consent
• •Glioblastoma leptomeningeal dissemination
• •Congestive heart failure classified as New York Heart Association (NYHA) Class 2 or higher; Unstable angina (symptoms of angina at rest) or new onset angina ≤3 months prior to screening; myocardial infarction \<6 months prior to 'start of study treatment; cardiac arrhythmias requiring antiarrhythmic therapy, with the exception of beta-blockers or digoxin; uncontrolled hypertension (systolic blood pressure \[SBP\]\>140 mmHg or diastolic blood pressure \[DBP\] \>90 mmHg) despite optimal medical management.
• •Arterial thrombotic or embolic events such as stroke and/or transient ischemic attacks) or
• •Pulmonary embolism in the 6 months prior to the start of study treatment
• •Ongoing infection with grade 2 or higher severity (NCI-CTCAE v 5.0)
• •Known history of human immunodeficiency virus (HIV) infection; hepatitis B or C active or chronic requiring treatment with antiviral therapy
• •History of organ allotransplantation
• •Evidence or history of any bleeding diathesis (including mild hemophilia), regardless of its severity;
• •Injuries, ulcers or bone fractures that have not fully resolved.
• •Renal failure requiring hemodialysis or peritoneal dialysis
• •Presenting interstitial lung disease with ongoing signs and symptoms at the time informed consent is obtained.
• •Persistent proteinuria \>3.5 g/24 hours as measured by urinary protein-creatinine ratio from a urine sample (≥ Grade 3, NCI-CTCAE v 5.0). CTCAE 5.0 is also available in Appendix 1.