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

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