Clinical trial NCT05793489: Prospective Double Arm Randomized Trial: WBRT Alone and WBRT Plus Silibinin
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Brain Metastases, Adult
Keywords: Brain Metastases
WBRT
Silibinin
Lead sponsor: Istituto Clinico Humanitas
Sponsor class: OTHER
Collaborators: name: health4u S.R.L
First posted: 2023-03-31
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective double arm randomized trial
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Overall Survival
timeFrame: 12 months
Secondary outcomes:
measure: Toxicity in term of use of corticosteroid therapy
timeFrame: 12 months
measure: Brain Distant Failure (BDF)
timeFrame: 12 months
measure: Progression Free Survival (PFS)
timeFrame: 12 months
Other outcomes:
Locations:
city: Rozzano
country: Italy
facility: IRCCS Humanitas Research Hospital
state: Milano
Study officials:
References: