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

Brain Metastases, Adult Clinical Trial

Official title:

Prospective Double Arm Randomized Trial for Patients With Multiple Brain Metastasis and/or Leptomeningeal Carcinomatosis: Comparison of WBRT Alone and WBRT Plus Silibinin (Sillbrain)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05793489
• Other study ID #: 3406
• Status: Recruiting
• Phase: N/A
• Start date: March 6, 2023
• Est. completion date: March 30, 2026

Study information

• Verified date: April 2023
• Source: Istituto Clinico Humanitas
• Contact: Elena Clerici
• Phone: 0282247310
• Email: elena.clerici[@]humanitas.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: March 30, 2026
• Est. primary completion date: March 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Metastases, Adult
• Brain Neoplasms
• Neoplasm Metastasis

Intervention

Other:
• 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.

Locations

Country	Name	City	State
Italy	IRCCS Humanitas Research Hospital	Rozzano	Milano

Sponsors (1)

Lead Sponsor	Collaborator
Istituto Clinico Humanitas

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Outcome will be evaluated in months	12 months
Secondary	Toxicity in term of use of corticosteroid therapy	Outcome will be evaluated in term of use or not of corticosteroids	12 months
Secondary	Brain Distant Failure (BDF)	Outcome will be evaluated in months	12 months
Secondary	Progression Free Survival (PFS)	Outcome will be evaluated in months	12 months