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

Launched by ISTITUTO ONCOLOGICO VENETO IRCCS · May 8, 2025

Keywords

ClinConnect Summary

This clinical trial is investigating the effects of a substance called silibinin when given alongside standard treatments for patients with a specific type of brain cancer called glioblastoma. Glioblastoma is a fast-growing tumor that affects the brain, and this study focuses on patients whose tumors are positive for a protein called STAT3 and do not have mutations in another gene called IDH. Participants in the trial will receive radiation therapy and a chemotherapy drug called temozolomide, along with either silibinin or a placebo (a substance with no active treatment) for a period of time. The goal is to see if adding silibinin can improve outcomes for these patients.

To be eligible for this trial, patients must be at least 18 years old and have a confirmed diagnosis of glioblastoma. They should also have their tumor tissue tested to ensure it expresses the STAT3 protein and must start treatment within seven weeks after surgery. Participants will need to have stable health and meet certain laboratory test requirements. Throughout the trial, patients can expect regular check-ups and assessments to monitor their health and response to treatment. It’s important to note that this trial is not yet recruiting participants, so interested patients will need to wait until it begins.

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ALL

Eligibility criteria

• 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 (centralized)
• • 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
• 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.