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

NCT ID: NCT05793489

Last Updated: 2025-04-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-06
• Study Completion Date: 2026-03-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

WBRT + Silibinin

Patients undergo WBRT concomitant to Silibinin

Group Type: EXPERIMENTAL

Silibinin

Intervention Type: 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

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Silibinin

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

health4u S.R.L

UNKNOWN

Sponsor Role: collaborator

Istituto Clinico Humanitas

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

IRCCS Humanitas Research Hospital

Rozzano, Milano, Italy

Countries

Italy

Other Identifiers

3406

Identifier Type: -

Identifier Source: org_study_id