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Silibinin with chemoradiotherapy and maintenance temozolomide for STAT3-positive, IDH wild-type glioblastoma

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

Not applicable Interventional Istituto Oncologico Veneto IRCCS · NCT06964815

This trial tests whether adding silibinin to standard chemoradiotherapy and maintenance temozolomide helps people with newly diagnosed STAT3-positive, IDH wild-type glioblastoma.

Quick facts

PhaseNot applicable
Study typeInterventional
Enrollment110 (estimated)
Ages18 Years to 99 Years
SexAll
SponsorIstituto Oncologico Veneto IRCCS Academic / other
Drugs / interventionsChemotherapy, immunotherapy
Locations16 sites (Bologna, BO and 15 other locations)
Trial IDNCT06964815 on ClinicalTrials.gov

What this trial studies

This is a multicenter, double-blind, placebo-controlled, randomized 1:1 trial enrolling patients with newly diagnosed, STAT3-positive, IDH wild-type glioblastoma. Participants receive standard concomitant radiotherapy (60 Gy in 30 fractions) plus temozolomide 75 mg/m2 with either silibinin or placebo (two sachets/day), followed by maintenance temozolomide (150–200 mg/m2 days 1–5 every 28 days) combined with silibinin/placebo given daily on days 1–28 for 6–12 cycles. Treatment may be continued until disease progression at the physician's discretion. Randomization is stratified by type of surgery, MGMT methylation status, and ECOG performance status.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) with newly diagnosed, histologically confirmed IDH wild-type glioblastoma that is pSTAT3-positive, who have not progressed after surgery, have ECOG 0–2, adequate organ function, and can start chemoradiotherapy within seven weeks of surgery.

Not a fit: Patients unlikely to benefit include those with IDH-mutant or STAT3-negative tumors, those with postoperative progression, or those with poor performance status or inadequate organ function.

Why it matters

Potential benefit: If successful, adding silibinin could slow tumor progression and potentially extend progression-free and overall survival in STAT3-positive, IDH wild-type glioblastoma patients.

How similar studies have performed: Preclinical and early-phase clinical data suggest STAT3-targeting approaches like silibinin have biological activity, but randomized placebo-controlled evidence in glioblastoma is currently limited.

Eligibility criteria

Show full inclusion / exclusion 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. 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

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.

Where this trial is running

Bologna, BO and 15 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions GlioblastomaIDH Wild-type and STAT3-positive GlioblastomaIDH wild-type and STAT3-positive glioblastomasilibinintemozolomideplacebo
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.