Brain Metastases, AdultNCT05793489
Prospective Double Arm Randomized Trial: WBRT Alone and WBRT Plus Silibinin
A study testing Silibinin in people with Brain Metastases, Adult, run by Istituto Clinico Humanitas at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases, Adult
- What is being tested?
- Silibinin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteItaly
- Study dates
- 6 Mar 2023to 30 Mar 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Prior WBRT
- KPS < 60
- Diagnosis of Lymphoproliferative disease
- Pregnant women
Trial locations and contacts
1 site in 1 country.
About this study
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)
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
- Being tested
- Silibinin
- Keywords
- Brain Metastases, WBRT, Silibinin
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SilibininOther
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.
| Study group | Role | What they receive |
|---|---|---|
| WBRT + Silibinin | Experimental | Patients undergo WBRT concomitant to Silibinin Receives: Other: Silibinin |
| WBRT | No intervention | Patients undergo WBRT alone, total dose of 30 Gy in 10 fractions. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Outcome will be evaluated in months
Measured: 12 months
Secondary outcomes (3)
Toxicity in term of use of corticosteroid therapy
Outcome will be evaluated in term of use or not of corticosteroids
Measured: 12 months
Brain Distant Failure (BDF)
Outcome will be evaluated in months
Measured: 12 months
Progression Free Survival (PFS)
Outcome will be evaluated in months
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2023
- Study start6 Mar 2023
- Primary completion4 Apr 2025
- Study completion30 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain Metastases, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective double arm randomized trial
- Masking
- None (open label)
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Collaborators
- health4u S.R.L
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05793489
- Sponsor's protocol ID
- 3406
- Status last verified
- Apr 2025
- First submitted
- 20 Mar 2023
- Last updated
- 24 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05793489
- Acronym / sponsor ID
- 3406
- Conditions
- Brain Metastases, Adult
- Keywords
- Brain Metastases, WBRT, Silibinin
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Collaborators
- health4u S.R.L
- Study start
- 6 Mar 2023 (actual)
- Primary completion
- 4 Apr 2025 (actual)
- Study completion
- 30 Mar 2026 (estimated)
- First posted
- 31 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective double arm randomized trial
| Arm | Type | Receives |
|---|---|---|
| WBRT + Silibinin | Experimental | Other: SilibininPatients undergo WBRT concomitant to Silibinin |
| WBRT | No intervention | –Patients undergo WBRT alone, total dose of 30 Gy in 10 fractions. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- Prior WBRT
- KPS < 60
- Diagnosis of Lymphoproliferative disease
- Pregnant women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SilibininWBRT 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. | Other | WBRT + Silibinin |
Primary outcome
Overall Survival
Time frame: 12 months
Outcome will be evaluated in months
3 secondary outcomes
Toxicity in term of use of corticosteroid therapy
Time frame: 12 months
Brain Distant Failure (BDF)
Time frame: 12 months
Progression Free Survival (PFS)
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Silibinin in people with Brain Metastases, Adult, run by Istituto Clinico Humanitas at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2025.