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

NCT06964815 | Recruiting

• 1 other identifier: IOV-GB-01-2024-STRONG
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 16

Brief Summary

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)

Conditions

Glioblastoma; IDH Wild-type and STAT3-positive Glioblastoma

Keywords

Glioblastoma; IDH wild-type and STAT3-positive glioblastoma; silibinin; temozolomide; placebo

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Evaluation of Progression Free Survival (PFS) in patients with newly diagnosed IDH wild-type and STAT3-positive glioblastoma using silibinin 2 sachets per day (1g/day), during chemoradiotherapy and maintenance treatment with temozolomide, compared with placebo. The progression free survival (PFS) will be determined as the time from the date of randomization to the date of disease progression determined using RANO 2.0 criteria or to the date of death, whichever occurs first. Patients without a PFS event at the time of analysis will be censored at the date of last assessment.

  Through study completion, an average of 2 years

Secondary Outcomes (7)

• Liver Toxicity

  Through study completion, an average of 2 years

• Liver Toxicity

  Through study completion, an average of 2 years

• Liver Toxicity

  Through study completion, an average of 2 years

• 6/9-months Progression Free Survival (6/9m-PFS)

  Through study completion, an average of 2 years

• Objective Response Rate (ORR)

  Through study completion, an average of 2 years

Study Arms (2)

Silbrain_Experimental Arm

EXPERIMENTAL

Concomitant radiotherapy (60 gy in 30 fractions) + temozolomide 75mg/mq + silibinin 2 sachets/day dissolved in water throughout concomitant treatment followed by temozolomide cp, 150 mg/m2-200mg/m2, g1-5 q28d + silibinin 2 sachets/day dissolved in water, day 1-28, q28d for 6cycles. Silibinin will be continued until disease progression or up to 24 months. In patients who develop progression during temozolomide treatment, administration of silibinin will be continued for up to 6 months after the last dose of temozolomide.

Dietary Supplement: Silibinin as STAT3 inhibitor

Placebo_Control Arm

PLACEBO COMPARATOR

Concomitant radiotherapy (60 gy in 30 fractions) + temozolomide 75mg/mq + placebo 2 sachets/day dissolved in water throughout concomitant treatment followed by temozolomide cp, 150 mg/m2-200mg/m2, g1-5 q28d + placebo 2 sachets/day dissolved in water, day 1-28, q28d for 6 cycles. Silibinin/Placebo may be continued until disease progression at the discretion of the physician. Silibinin/Placebo will be continued until disease progression or up to 24 months. In patients who develop progression during temozolomide treatment, administration of silibinin (or placebo) will be continued for up to 6 months after the last dose of temozolomide.

Other: Placebo

Interventions

Silibinin as STAT3 inhibitor DIETARY_SUPPLEMENT

Sillbrain will be available as granulate in sachets of 3.7g and it will be administered twice a day during chemo-radiotherapy and day 1-28 in maintenance phase every cycle. Each 3.7 g sachet of Sillbrain contains 500 mg silibinin. Every patient will assume 2 sachets/day for a total of 1 g/day of silibinin.

Silbrain_Experimental Arm

Placebo OTHER

Placebo will be available as granulate in sachets of 3.7g and it will be administered twice a day during chemo-radiotherapy and day 1-28 in maintenance phase every cycle. Every patient will assume 2 sachets/day for a total of 1 g/day of placebo.

Placebo_Control Arm

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Istituto Oncologico Veneto IRCCS: lead

Study Sites (16)

IRCCS Istituto delle Scienze Neurologiche di Bologna

Bologna, BO, 40139, Italy

NOT YET RECRUITING

IRST Dino Amadori

Meldola, FC, 47014, Italy

NOT YET RECRUITING

Azienda Ospedaliero Universitaria Policlinico "G. Rodolico - San Marco "

Catania, Italia/Catania, 95123, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria - Careggi

Florence, Italia/FI, 50134, Italy

NOT YET RECRUITING

ARNAS G.Brotzu P.O Armando Businco

Cagliari, Italy/Cagliari, 09047, Italy

NOT YET RECRUITING

USL Nord Ovest Toscana - Livorno

Livorno, Italy/Livorno, 57124, Italy

NOT YET RECRUITING

Ospedale del Mare, ASL Napoli1 Centro

Napoli, italy/Napoli, 80147, Italy

NOT YET RECRUITING

Istituto Oncologico Veneto

Padua, Italy/Padova, 35128, Italy

RECRUITING

Istituto Neurologico Nazionale a Carattere Scientifico IRCCS - Fondazione Mondino

Pavia, Italy/Pavia, 27100, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria G.Martino

Messina, ME, 98124, Italy

NOT YET RECRUITING

Istituto Tumori Regina Elena IRCCS

Roma, RM, 00128, Italy

NOT YET RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, RM, Italy

NOT YET RECRUITING

Policlinico San Martino - Genova

Genova, Italy

NOT YET RECRUITING

Ospedale A. Manzoni Lecco

Lecco, 23900, Italy

NOT YET RECRUITING

Humanitas Cancer Center

Milan, 20089, Italy

NOT YET RECRUITING

IRCCS Ospedale Galeazzi Sant'Ambrogio

Milan, 20157, Italy

NOT YET RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

Silybin

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Silymarin; Flavonolignans; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Giuseppe Lombardi, MD

CONTACT

0498215888; giuseppe.lombardi@iov.veneto.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2025
• First Posted: May 9, 2025
• Study Start: November 12, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: December 2, 2025

Record last verified: 2025-09

Locations

IT (16)