SILibinin in NSCLC and BC Patients With Single Brain METastasis (SILMET)

NCT05689619 | Recruiting DMC

• 1 other identifier: SILMET_0107665
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 6

Brief 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).

Conditions

Brain Metastases, Adult; Non Small Cell Lung Cancer; Breast Cancer

Keywords

Silibinin; Single Brain Metastasis; Non-small-cell Lung Cancer; Breast Cancer

Outcome Measures

Primary Outcomes (1)

• intracranial local recurrence

  to investigate whether silibinin delay the intracranial local recurrence in comparison to placebo

  up to 12-24 months

Secondary Outcomes (6)

• intracranial distant recurrence

  up to 12-24 months

• Intracranial progression-free survival

  up to 12-24 months

• Overall progression-free survival

  up to 12-24 months

• Overall survival

  up to 24 months

• Assessment of the quality of life of brain metastasis patients

  8 weeks, 16 weeks, 24 weeks, 32 weeks, 40 weeks, 48 weeks, 56 weeks, thereafter every 24 weeks

Study Arms (2)

Silibinin

EXPERIMENTAL

Silibinin (STAT3 inhibitor) 1 g/day taken orally every day

Dietary Supplement: Silibinin

Placebo

PLACEBO COMPARATOR

Placebo 1 g/day taken orally every day

Other: Placebo

Interventions

Silibinin DIETARY_SUPPLEMENT

Silibinin 1 g/day taken orally plus standard systemic therapy for NSCLC or BC

Also known as: Sillbrain

Silibinin

Placebo OTHER

Placebo 1 g/day taken orally plus standard systemic therapy for NSCLC or BC

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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:

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• A.O.U. Città della Salute e della Scienza: lead

Study Sites (6)

Unità Operativa di Oncologia Medica 2, IRCCS Ospedale Policlinico San Martino di Genova

Genova, Italy

NOT YET RECRUITING

Neurosurgery Unit, Department of Biomedical, Dental Science and Morphological and Functional Images, University of Messina

Messina, Italy

RECRUITING

Institute of Neurosurgery, IRCCS Fondazione Policlinico Universitario Agostino Gemelli, Catholic University

Rome, Italy

NOT YET RECRUITING

Neuro-Oncology Unit, IRCCS Regina Elena National Cancer Institute

Rome, Italy

NOT YET RECRUITING

Precision Medicine in Breast Cancer Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Italy

NOT YET RECRUITING

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Turin, 10126, Italy

RECRUITING

Related Publications (1)

• 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.

  PMID: 29892069 BACKGROUND

MeSH Terms

Conditions

Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Breast Neoplasms

Interventions

Silybin

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Silymarin; Flavonolignans; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Pierangela Botta

CONTACT

+390116334904; botta.neuro.oncologia@gmail.com

Alessia Pellerino, M.D., Ph.D.

CONTACT

+390116334904; alessia.pellerino85@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Ph.D.

Model Details: Randomized (1:1) phase 2 trial

Study Record Dates

• First Submitted: January 4, 2023
• First Posted: January 19, 2023
• Study Start: September 1, 2023
• Primary Completion: September 1, 2025
• Study Completion (Estimated): September 1, 2027
• Last Updated: December 15, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

IT (6)