Prospective Double Arm Randomized Trial: WBRT Alone and WBRT Plus Silibinin

NCT05793489 | Active Not Recruiting

• 1 other identifier: 3406
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The occurrence of brain metastases (BMs) is increasing given the availability of a more accurate radiological imaging such as MRI for detecting also small brain lesions and the most effective systemic therapy able to control extracranial disease. Although, the new target therapy and immunotherapy has proven to be effective on brain metastasis too, a subgroup of patients shows prove themselves unresponsive to medical treatment. A further subgroup of patients exhibit diffuse brain disease for the presence of multiple brain lesion (\>10 BMs) or leptomeningeal carcinomatosis. Among these patients the most treatment employed is represented by whole brain RT. Since the 1950s, whole-brain radiation therapy (WBRT) has been the most widely used treatment for patients with multiple brain metastases, given its effectiveness in palliation, widespread availability, and ease to delivery. However, the median overall survival recorded is restricted to 3 months, on the average. A better understanding of the molecular and cellular mechanisms underlying brain metastasis might be expected to lead to improvements in the overall survival rate for these patients. Recent studies have revealed complex interactions between metastatic cancer cells and their microenvironment in the brain. Priego et al. describe that brain metastatic cells induce and maintain the co-option of a pro-metastatic program driven by signal transducer and activator of transcription 3 (STAT3) in a subpopulation of reactive astrocytes surrounding metastatic lesions. In patients, active STAT3 in reactive astrocytes correlates with reduced survival from diagnosis of intracranial metastases. Blocking STAT3 signaling in reactive astrocytes reduces experimental brain metastasis from different primary tumor sources, even at advanced stages of colonization. Silibinin (or silybin) is a natural polyphenolic flavonoid isolated from seed extracts of the herb milk thistle (Silybum marianum). Silibinin has been shown to impair STAT3 activation. Preclinical studies show that Silibinin has an anticancer effects in vitro and in vivo. Based on this background, the investigators designed a double arm randomized trial evaluating the benefit of Silibinin (in the form of marketed supplement) associated to WBRT respect to WBRT alone.

Conditions

Brain Metastases, Adult

Keywords

Brain Metastases; WBRT; Silibinin

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Outcome will be evaluated in months

  12 months

Secondary Outcomes (3)

• Toxicity in term of use of corticosteroid therapy

  12 months

• Brain Distant Failure (BDF)

  12 months

• Progression Free Survival (PFS)

  12 months

Study Arms (2)

WBRT + Silibinin

EXPERIMENTAL

Patients undergo WBRT concomitant to Silibinin

Other: Silibinin

WBRT

NO INTERVENTION

Patients undergo WBRT alone, total dose of 30 Gy in 10 fractions.

Interventions

Silibinin OTHER

WBRT will be concomitant to Silibinin. Silibinin at dose of 500 mg must be administrated twice a day for the first month, after once a day continuously. Total dose and fractionation of WBRT: 30 Gy in 10 fractions.

WBRT + Silibinin

Eligibility Criteria

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

You may qualify if:

• Age \>18 years
• Histological or cytological confirmation of solid tumor malignancy
• Clinical indication for whole brain radiotherapy
• Karnofsky performance status (KPS) ≥60
• Written informed consent

You may not qualify if:

• Prior WBRT
• KPS \< 60
• Diagnosis of Lymphoproliferative disease
• Pregnant women

Sponsors & Collaborators

• Istituto Clinico Humanitas: lead
• health4u S.R.L: collaborator

Study Sites (1)

IRCCS Humanitas Research Hospital

Rozzano, Milano, 20089, Italy

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Silybin

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

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

Study Design

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

Model Details: Prospective double arm randomized trial

Study Record Dates

• First Submitted: March 20, 2023
• First Posted: March 31, 2023
• Study Start: March 6, 2023
• Primary Completion: April 4, 2025
• Study Completion: March 30, 2026
• Last Updated: April 24, 2025

Record last verified: 2025-04

Locations

IT (1)