Brain Metastases, AdultSILMETNCT05689619
SILibinin in NSCLC and BC Patients With Single Brain METastasis (SILMET)
A study testing Silibinin in people with Brain Metastases, Adult and Non Small Cell Lung Cancer, run by A.O.U. Città della Salute e della Scienza at 6 sites in Italy.
Trial summary
This study aims to evaluate the efficacy of silibinin in preventing recurrence in the brain after complete resection of a brain metastasis (BM) from non-small-cell lung cancer (NSCLC) or breast cancer (BC). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Brain Metastases, Adult, Non Small Cell Lung Cancer, Breast Cancer
- What is being tested?
- Silibinin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 6 sitesItaly
- Study dates
- 1 Sep 2023to 1 Sep 2027
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed BM from NSCLC or BC by local pathology
- Single BM (maximum diameter of 3 cm) on MRI before surgery
- Complete surgical resection (MRI-verified within 14 days prior randomization)
- pSTAT3 score in reactive astrocytes of peritumoral tissue confirmed by local or central assessment
- patient must have recovered from the effects of surgery, including post-operative infection, suture/stample removal from brain surgery and wound healing before randomization
- ≥ 18 - 70 years of age
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- Karnofsky performance status ≥ 70 at assessment ≤ 14 days prior to randomization
- patient has adequate bone marrow, renal, and hepatic function ≤ 21 days prior to randomization as follows:
- absolute neutrophil count (ANC) ≥ 1500/mm3
- platelets ≥ 100000/ mm3
- Hemoglobin ≥ 9.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin ≥ 9.0 g/dl is acceptable)
- renal function: calculated creatinine clearance ≥ 30 ml/min by the Cockcroft-Gault formula
- hepatic function: total bilirubin ≤ 1.5 times upper limit of normal (ULN), aspartate aminotransferase (AST), and alanine transferase (ALT) ≤ 3 times ULN. Subjects with Gilbert's syndrome documented in medical history may be enrolled if total bilirubin is < 3 times ULN
- Electrocardiogram (ECG) without evidence of acute cardiac ischemia ≤ 21 days prior to randomization
- Female subject of childbearing potential (i.e. those who are not postmenopausal for at least 1 year or surgically sterile by bilateral salpingectomy, bilateral oophorectomy or hysterectomy) should practice at least one accepted method of birth control listed below during study entry, for the entire duration of the study and for at least 6 months after treatment with silibinin has ended. Male subjects should practice at least one accepted method of birth control listed below during study entry, for the entire duration of the study and for at least 6 months after treatment with silibinin has ended. If using a condom, practice at least one other method of birth control listed below during the study for at least 6 months after silibinin treatment:
- Combined (estrogen and progesterone contained) hormonal contraception (oral, intravaginal, transdermal) associated with the inhibition of ovulation
- Progesterone-only hormonal contraception (oral, intravaginal, transdermal) associated with the inhibition of ovulation
- Bilateral tubal occlusion/ligation
- True abstinence: refraining from heterosexual intercourse when this is in line with the preferred and usual lifestyle of the subject
- A vasectomized male subject or a vasectomized partner of a female subject
- Intrauterine device, IUD (females)
- Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream) unless not deemed acceptable as highly effective contraception by local regulations
- Women of child-bearing potential must have a negative pregnancy test (urine o serum) within 7 days prior the randomization
- Must voluntarily sign and date informed consent form, for both tumor tissue biomarker testing and study participation, approved by an Independent Ethic Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures
Who cannot join
- Absence of expression of STAT3 on the reactive astrocytes of brain metastases
- Incomplete surgical resection and/or diameters > 3 centimeters of brain metastasis before surgery
- Brain metastases that previously received any type of radiation therapy
- Progressive systemic disease requiring a change of the antineoplastic therapy
- Prior invasive malignancy (except for non-melanomatous skin cancer, oral cavity, or cervix) unless disease free for ≥ 2 years
- Prior, concomitant, or planned treatment with experimental agents
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- Patients has had major immunologic reaction
- Patient has had a history of hypersensitivity to silibinin or excipient
- Patient is unsuitable to receive steroids
- Patient is a lactating or pregnant female
- Severe, active co-morbidity, defined as follows:
- Severe hepatic impairment (Child-Pugh C or higher [score of 10 or higher]); subject with mild or moderate hepatic impairment (Child-Pugh score of 5-9) may be eligible for treatment
- Unstable angina and/or congestive heart failure within the last 6 months
- Transmural myocardial infarction within the last 6 months
- Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations ≥ 2 mm using the analysis of an EKG performed within 21 days prior to enrollment
- New York Heart Association grade2 or greater congestive heart failure requiring hospitalization within 12 months prior to enrollment
- History of stroke, cerebral vascular accident or transient ischemic attack within 6 months
- Serious and inadequately controlled cardiac arrhythmia
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of enrollment
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of enrollment
- Subject with clinically defined Acquired Immune-Deficiency Syndrome (AIDS)-defining illness. This is necessary to ensure subjects are likely to be able to receive silibinin plus standard of care according to the systemic disease
- Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the Investigator may put the subject at high risk of toxicity
- Any other major medical illnesses or psychiatric impairments that in the Investigator's opinion will prevent administrations or completion of protocol therapy
- Patient treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study except intra-operative therapy to guide resection or experimental imaging without therapeutic intent
- Inability to undergo contrast-enhanced MRI scans
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
Italy6 sites, 6 recruiting
- Not yet recruiting
Unità Operativa di Oncologia Medica 2, IRCCS Ospedale Policlinico San Martino di Genova
Genova
Elisa Bennicelli, M.D., elisa.bennicelli@hsanmartino.it
- Recruiting
Neurosurgery Unit, Department of Biomedical, Dental Science and Morphological and Functional Images, University of Messina
Messina
Filippo Flavio Angileri
Maria Caffo
- Not yet recruiting
Institute of Neurosurgery, IRCCS Fondazione Policlinico Universitario Agostino Gemelli, Catholic University
Rome
Alessandro Olivi
- Not yet recruiting
Neuro-Oncology Unit, IRCCS Regina Elena National Cancer Institute
Rome
Andrea Pace
- Not yet recruiting
Precision Medicine in Breast Cancer Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Rome
Alessandra Fabi
- Recruiting
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Turin, 10126
Alessia Pellerino, M.D., Ph.D, +390116334904, alessia.pellerino85@gmail.com
Pierangela Botta, +390116334904, botta.neuro.oncologia@gmail.com
About this study
Official title: A Phase 2 Randomized, Multicenter Trial on Silibinin To Prevent Intracranial Recurrence After Gross-Total Resection of Single Brain Metastasis From Non-Small Cell Lung Cancer or Breast Cancer
This study aims to evaluate the efficacy of silibinin in preventing recurrence in the brain after complete resection of a brain metastasis (BM) from non-small-cell lung cancer (NSCLC) or breast cancer (BC).
Read the detailed description
This is the first placebo-controlled study evaluating the efficacy of silibinin as STAT3 inhibitor in preventing recurrence in the brain after gross-total resection of a brain metastasis (BM) from non-small-cell lung cancer (NSCLC) or breast cancer (BC).
Participants will be randomized 1:1 to silibinin 1 g/day taken orally in comparison with oral placebo 1 g/day. A contrast-enhanced brain MRI will be performed every 8 weeks to evaluate intracranial local and distance recurrence
- Being tested
- Silibinin, Placebo
- Keywords
- Silibinin, Single Brain Metastasis, Non-small-cell Lung Cancer, Breast Cancer
- Medical subject headings
- Brain Neoplasms, Carcinoma, Non-Small-Cell Lung, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SilibininDietary supplement
Also called Sillbrain
Silibinin 1 g/day taken orally plus standard systemic therapy for NSCLC or BC
PlaceboOther
Placebo 1 g/day taken orally plus standard systemic therapy for NSCLC or BC
| Study group | Role | What they receive |
|---|---|---|
| Silibinin | Experimental | Silibinin (STAT3 inhibitor) 1 g/day taken orally every day Receives: Dietary Supplement: Silibinin |
| Placebo | Placebo comparator | Placebo 1 g/day taken orally every day Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
intracranial local recurrence
to investigate whether silibinin delay the intracranial local recurrence in comparison to placebo
Measured: up to 12-24 months
Secondary outcomes (6)
intracranial distant recurrence
to investigate whether silibinin delay or avoid the intracranial distant recurrence in comparison to placebo
Measured: up to 12-24 months
Intracranial progression-free survival
intracranial local plus distant recurrence
Measured: up to 12-24 months
Overall progression-free survival
intracranial plus systemic PFS
Measured: up to 12-24 months
Overall survival
to investigate whether silibinin improve the overall survival in comparison to placebo
Measured: up to 24 months
Assessment of the quality of life of brain metastasis patients
EORTC QLQ-C30 and EORTC QLQ-BN20
Measured: 8 weeks, 16 weeks, 24 weeks, 32 weeks, 40 weeks, 48 weeks, 56 weeks, thereafter every 24 weeks
to determine incidence of adverse events
Measured: up to 12-24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2023
- Study start1 Sep 2023
- Primary completion1 Sep 2025 (estimated)
- Study completion1 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized (1:1) phase 2 trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- A.O.U. Città della Salute e della Scienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alessia Pellerino, A.O.U. Città della Salute e della Scienza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05689619
- Sponsor's protocol ID
- SILMET_0107665
- Acronym
- SILMET
- Status last verified
- Dec 2023
- First submitted
- 4 Jan 2023
- Last updated
- 15 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Principal Investigators will provide access to related study documents (e.g. protocol, statistical analysis plan, clinical study report) upon request from qualified researchers, and subjects with certain criteria, conditions, and exception that will be discussed with PI
Publications
Priego N, Zhu L, Monteiro C, Mulders M, Wasilewski D, Bindeman W, Doglio L, Martinez L, Martinez-Saez E, Ramon Y Cajal S, Megias D, Hernandez-Encinas E, Blanco-Aparicio C, Martinez L, Zarzuela E, Munoz J, Fustero-Torre C, Pineiro-Yanez E, Hernandez-Lain A, Bertero L, Poli V, Sanchez-Martinez M, Menendez JA, Soffietti R, Bosch-Barrera J, Valiente M. STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis. Nat Med. 2018 Jul;24(7):1024-1035. doi: 10.1038/s41591-018-0044-4. Epub 2018 Jun 11.
PubMed 29892069
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Randomized, Multicenter Trial on Silibinin To Prevent Intracranial Recurrence After Gross-Total Resection of Single Brain Metastasis From Non-Small Cell Lung Cancer or Breast Cancer
- ClinicalTrials.gov ID
- NCT05689619
- Acronym / sponsor ID
- SILMET / SILMET_0107665
- Keywords
- Silibinin, Single Brain Metastasis, Non-small-cell Lung Cancer, Breast Cancer
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- A.O.U. Città della Salute e della ScienzaUniversity, hospital or other
- Study start
- 1 Sep 2023 (actual)
- Primary completion
- 1 Sep 2025 (estimated)
- Study completion
- 1 Sep 2027 (estimated)
- First posted
- 19 Jan 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.
This study aims to evaluate the efficacy of silibinin in preventing recurrence in the brain after complete resection of a brain metastasis (BM) from non-small-cell lung cancer (NSCLC) or breast cancer (BC).
Detailed description
This is the first placebo-controlled study evaluating the efficacy of silibinin as STAT3 inhibitor in preventing recurrence in the brain after gross-total resection of a brain metastasis (BM) from non-small-cell lung cancer (NSCLC) or breast cancer (BC).
Participants will be randomized 1:1 to silibinin 1 g/day taken orally in comparison with oral placebo 1 g/day. A contrast-enhanced brain MRI will be performed every 8 weeks to evaluate intracranial local and distance recurrence
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Randomized (1:1) phase 2 trial
| Arm | Type | Receives |
|---|---|---|
| Silibinin | Experimental | Dietary Supplement: SilibininSilibinin (STAT3 inhibitor) 1 g/day taken orally every day |
| Placebo | Placebo comparator | Other: PlaceboPlacebo 1 g/day taken orally every day |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Histologically confirmed BM from NSCLC or BC by local pathology
- Single BM (maximum diameter of 3 cm) on MRI before surgery
- Complete surgical resection (MRI-verified within 14 days prior randomization)
- pSTAT3 score in reactive astrocytes of peritumoral tissue confirmed by local or central assessment
- patient must have recovered from the effects of surgery, including post-operative infection, suture/stample removal from brain surgery and wound healing before randomization
Key exclusion criteria (25 listed)
- Absence of expression of STAT3 on the reactive astrocytes of brain metastases
- Incomplete surgical resection and/or diameters > 3 centimeters of brain metastasis before surgery
- Brain metastases that previously received any type of radiation therapy
- Progressive systemic disease requiring a change of the antineoplastic therapy
- Prior invasive malignancy (except for non-melanomatous skin cancer, oral cavity, or cervix) unless disease free for ≥ 2 years
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 |
|---|---|---|
| SilibininAlso: SillbrainSilibinin 1 g/day taken orally plus standard systemic therapy for NSCLC or BC | Dietary supplement | Silibinin |
| PlaceboPlacebo 1 g/day taken orally plus standard systemic therapy for NSCLC or BC | Other | Placebo |
Primary outcome
intracranial local recurrence
Time frame: up to 12-24 months
to investigate whether silibinin delay the intracranial local recurrence in comparison to placebo
6 secondary outcomes
intracranial distant recurrence
Time frame: up to 12-24 months
Intracranial progression-free survival
Time frame: up to 12-24 months
Overall progression-free survival
Time frame: up to 12-24 months
Overall survival
Time frame: up to 24 months
Assessment of the quality of life of brain metastasis patients
Time frame: 8 weeks, 16 weeks, 24 weeks, 32 weeks, 40 weeks, 48 weeks, 56 weeks, thereafter every 24 weeks
to determine incidence of adverse events
Time frame: up to 12-24 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 15 Dec 2023.
- Background: PubMed 29892069Priego N, Zhu L, Monteiro C, Mulders M, Wasilewski D, Bindeman W, Doglio L, Martinez L, Martinez-Saez E, Ramon Y Cajal S, Megias D, Hernandez-Encinas E, Blanco-Aparicio C, Martinez L, Zarzuela E, Munoz J, Fustero-Torre C, Pineiro-Yanez E, Hernandez-Lain A, Bertero L, Poli V, Sanchez-Martinez M, Menendez JA, Soffietti R, Bosch-Barrera J, Valiente M. STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis. Nat Med. 2018 Jul;24(7):1024-1035. doi: 10.1038/s41591-018-0044-4. Epub 2018 Jun 11.
- Individual participant dataSharing planned: Yes. Principal Investigators will provide access to related study documents (e.g. protocol, statistical analysis plan, clinical study report) upon request from qualified researchers, and subjects with certain criteria, conditions, and exception that will be discussed with PI
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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.
6 sites 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 and Non Small Cell Lung Cancer, run by A.O.U. Città della Salute e della Scienza at 6 sites 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 24 inclusion and 25 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: looking for participants now, as of the sponsor's last update on 15 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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. Some participants in this study may receive a placebo. 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?
Contact Pierangela Botta (+390116334904, botta.neuro.oncologia@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
intracranial local recurrence (time frame: up to 12-24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05689619, which also lists 1 linked publication.
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 15 Dec 2023.