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 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
Parallel
Silibinin as STAT3 inhibitor
Dietary supplementSillbrain 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.
Placebo
Other interventionPlacebo 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.
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.
Liver Toxicity
Evaluation of liver toxicity. Assessment of liver toxicity will be derived from the assay of alanine aminotransferase (ALT) weekly during concomitant radio-chemotherapy treatment and monthly during maintenance temozolomide treatment, using the CTCAE v5.0 system to determine the degree of toxicity
Liver Toxicity
Evaluation of liver toxicity. Assessment of liver toxicity will be derived from the assay of total and direct blood bilirubin weekly during concomitant radio-chemotherapy treatment and monthly during maintenance temozolomide treatment, using the CTCAE v5.0 system to determine the degree of toxicity
Liver Toxicity
Evaluation of liver toxicity. Assessment of liver toxicity will be derived from the assay of aspartate aminotransferase (AST) weekly during concomitant radio-chemotherapy treatment and monthly during maintenance temozolomide treatment, using the CTCAE v5.0 system to determine the degree of toxicity
6/9-months Progression Free Survival (6/9m-PFS)
Evaluation of 6/9-months Progression Free Survival (6/9m-PFS). The progression free survival at 6/9 months (6/9m-PFS) will be determined as the percentage of patient with progression of disease at 6 and 9 months
Click on the lead sponsor to view all of their trials.
