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

NCT ID: NCT05689619

Last Updated: 2023-12-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-01

Study Completion Date

2027-09-01

Brief Summary

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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

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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

Conditions

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Brain Metastases, Adult Non Small Cell Lung Cancer Breast Cancer

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized (1:1) phase 2 trial
Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Silibinin

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

Group Type EXPERIMENTAL

Silibinin

Intervention Type DIETARY_SUPPLEMENT

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

Placebo

Placebo 1 g/day taken orally every day

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

Interventions

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Silibinin

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

Intervention Type DIETARY_SUPPLEMENT

Placebo

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

Intervention Type OTHER

Other Intervention Names

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Sillbrain

Eligibility Criteria

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Inclusion Criteria

* 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:

1. absolute neutrophil count (ANC) ≥ 1500/mm3
2. platelets ≥ 100000/ mm3
3. Hemoglobin ≥ 9.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin ≥ 9.0 g/dl is acceptable)
4. renal function: calculated creatinine clearance ≥ 30 ml/min by the Cockcroft-Gault formula
5. 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

Exclusion Criteria

* 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
* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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A.O.U. Città della Salute e della Scienza

OTHER

Sponsor Role lead

Responsible Party

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Alessia Pellerino

M.D., Ph.D.

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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

Genova, , Italy

Site Status NOT_YET_RECRUITING

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

Messina, , Italy

Site Status RECRUITING

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

Rome, , Italy

Site Status NOT_YET_RECRUITING

Neuro-Oncology Unit, IRCCS Regina Elena National Cancer Institute

Rome, , Italy

Site Status NOT_YET_RECRUITING

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

Rome, , Italy

Site Status NOT_YET_RECRUITING

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Turin, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Pierangela Botta

Role: CONTACT

Phone: +390116334904

Email: [email protected]

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

Role: CONTACT

Phone: +390116334904

Email: [email protected]

Facility Contacts

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Elisa Bennicelli, M.D.

Role: primary

Filippo Flavio Angileri

Role: primary

Alessandro Olivi

Role: primary

Andrea Pace

Role: primary

Alessandra Fabi

Role: primary

Alessia Pellerino, M.D., Ph.D

Role: primary

Pierangela Botta

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 29892069 (View on PubMed)

Other Identifiers

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SILMET_0107665

Identifier Type: -

Identifier Source: org_study_id