Trial Title:
SILibinin in NSCLC and BC Patients With Single Brain METastasis (SILMET)
NCT ID:
NCT05689619
Condition:
Brain Metastases, Adult
Non Small Cell Lung Cancer
Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasm Metastasis
Brain Neoplasms
Silybin
Conditions: Keywords:
Silibinin
Single Brain Metastasis
Non-small-cell Lung Cancer
Breast Cancer
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Randomized (1:1) phase 2 trial
Primary purpose:
Prevention
Masking:
Triple (Participant, Care Provider, Investigator)
Intervention:
Intervention type:
Dietary Supplement
Intervention name:
Silibinin
Description:
Silibinin 1 g/day taken orally plus standard systemic therapy for NSCLC or BC
Arm group label:
Silibinin
Other name:
Sillbrain
Intervention type:
Other
Intervention name:
Placebo
Description:
Placebo 1 g/day taken orally plus standard systemic therapy for NSCLC or BC
Arm group label:
Placebo
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).
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
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Unità Operativa di Oncologia Medica 2, IRCCS Ospedale Policlinico San Martino di Genova
Address:
City:
Genova
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Elisa Bennicelli, M.D.
Email:
elisa.bennicelli@hsanmartino.it
Facility:
Name:
Neurosurgery Unit, Department of Biomedical, Dental Science and Morphological and Functional Images, University of Messina
Address:
City:
Messina
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Filippo Flavio Angileri
Investigator:
Last name:
Maria Caffo
Email:
Sub-Investigator
Facility:
Name:
Institute of Neurosurgery, IRCCS Fondazione Policlinico Universitario Agostino Gemelli, Catholic University
Address:
City:
Rome
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Alessandro Olivi
Facility:
Name:
Neuro-Oncology Unit, IRCCS Regina Elena National Cancer Institute
Address:
City:
Rome
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Andrea Pace
Facility:
Name:
Precision Medicine in Breast Cancer Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Address:
City:
Rome
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Alessandra Fabi
Facility:
Name:
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Address:
City:
Turin
Zip:
10126
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Alessia Pellerino, M.D., Ph.D
Phone:
+390116334904
Email:
alessia.pellerino85@gmail.com
Contact backup:
Last name:
Pierangela Botta
Phone:
+390116334904
Email:
botta.neuro.oncologia@gmail.com
Start date:
September 1, 2023
Completion date:
September 1, 2027
Lead sponsor:
Agency:
A.O.U. Città della Salute e della Scienza
Agency class:
Other
Source:
A.O.U. Città della Salute e della Scienza
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05689619
