Hepatocellular carcinoma
Conditions
Interventions
Neoadjuvant therapy group:Tislelizumab combined with lenvatinib was treated for four cycles before surgery. After operation, tislelizumab combined with lenvatinib was treated for half a year
Adjuvant therapy group:After operation, tislelizumab combined with lenvatinib was treated for half a year
Sponsors
The first medical center of Chinese PLA general hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Provide written informed consent, comply with protocol-specified visits and procedures, understand and accept randomization. 2. Age =18 years old and =75 years old. 3. Histologically/cytologically confirmed HCC or meeting the American Association for Clinical Diagnosis of Liver Diseases (AASLD) clinical diagnostic criteria for HCC. 4. Meet at least one of the criteria for high-risk recurrence factors. (? Tumor thrombus in the second or third branch of portal vein (VP2/VP1); ? tumor thrombus in the first or second branch of hepatic vein (VV1/VV2); ? with isolated and limited to No.8 / No.12 lymph node metastasis; ? multiple tumors in the liver > 2 lesions; ? tumor > 5cm; ? the tumor is adjacent to the important vascular structures in the liver that must be preserved, and the tumor resection margin of 1cm or more cannot be guaranteed near the corresponding structures; Or adjacent organ and tissue invasion; ? the history of tumor rupture; Tumor markers were significantly increased, AFP> 400ng/ml, or PIVKA-II> 300mAu) 5. At least one measurable lesion, according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), without local treatment or with definite progression after local treatment. 6. Child-Pugh score =7 (Child-Pugh A/B). 7. ECOG performance status of 0 or 1. 8. Female subjects of childbearing age or male subjects whose sexual partner is a female of childbearing age are required to use effective contraception during the entire treatment period and 6 months after the treatment period. 9. Adequate organ and bone marrow function with laboratory values within 7 days prior to enrollment (no administration of blood components, cell growth factors, albumin, or other corrective medications within 14 days prior to laboratory testing), as follows: ? Blood routine: absolute neutrophil count (ANC) =1.5×109/L; platelet count (PLT) =75×109/L; hemoglobin (HGB) level =8.5 g/dL. ? Liver function: serum total bilirubin (TBIL) =3× upper limit of normal value (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =5×ULN; Serum albumin =28 g/L; alkaline phosphatase (ALP) =5×ULN. ? Renal function: serum creatinine (Cr) = 1.5×ULN or clearance of creatinine (CCr) = 50mL/min(Cockcroft-Gault formula); Urine routine showed urinary protein < 2+ 2. ? Coagulation function: International normalized ratio (INR) = 2 and activated partial thromboplastin time (APTT) = 1.5 times ULN.
Exclusion criteria
Exclusion criteria: 1. Contains fibroblastic layer hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, bile duct carcinoma and other components. 2. A history of hepatic encephalopathy or a history of liver transplantation. 3. Patients with hydrothorax, ascites and pericardial effusion with clinical symptoms or need drainage. 4. Acute or chronic active hepatitis b or c infection: HBV DNA>2000IU/ml or 104 /ml HCV RNA> 103 /ml HbsAg+ and HCVAb +. 5. Symptomatic central nervous metastasis. Patients with asymptomatic brain metastases or brain metastases whose symptoms are stable after treatment may participate in this study as long as they meet all the following criteriameasurable lesions outside the central nervous systemNo mesencephalon, pons, cerebellum, meninges, medulla oblongata, or spinal cord metastasesRemain clinically stable for at least 4 weeksGlucocorticoid therapy was discontinued two weeks before the first dose of the study drug. 6. Varicose bleeding of esophageal or gastric fundus caused by portal hypertension has occurred in the past 6 months. 7. Any life-threatening bleeding event that has occurred within the previous 3 months, including the need for blood transfusion, surgery or topical treatment, and continued medication. 8. Previous history of vte events, including myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep venous thrombosis, or any other serious thromboembolism, within 6 months. Except for those with stable thrombus after routine anticoagulant therapy, there are cases of catheter-derived thrombosis or superficial venous thrombosis. Preventive use of low dose aspirin and low molecular weight heparin is permitted. 9. Uncontrolled hypertension, systolic blood pressure >= 150mmHg or diastolic blood pressure >= 100mmHg after optimal medical treatment, hypertensive crisis or hypertensive encephalopathy history. 10. Symptomatic congestive heart failure (New York heart association grade II-IV). Symptomatic or poorly controlled arrhythmias. QT interval was prolonged, QTc > 450ms(male), QTc > 470ms(female). 11. Severe bleeding tendency or coagulation dysfunction, or receiving thrombolytic treatment. 12. A history of gastrointestinal perforations and/or fistulas, intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), inflammatory bowel disease or extensive bowel resection (partial colectomy or extensive small bowel resection with chronic diarrhea), crohn's disease, ulcerative colitis, or chronic diarrhea within 6 months. 13. History of interstitial pneumonia, drug pneumonia, idiopathic pneumonia or active pneumonia. Radiation therapy is permitted in the area of radioactive pneumonia. 14. Active tuberculosis (TB), who are receiving anti-tb treatment or who received anti-tb treatment within 1 year prior to the first study. 15. Human immunodeficiency virus (HIV) infection (HIV 1/2 antibody positive). 16. A severe infection that is active or clinically poorly controlled.Severe infections, including but not limited to hospitalization for infection, bacteremia, or complications of severe pneumonia, occurred 4 weeks before the first study. 17. Autoimmune disease requiring systematic treatment or a history of the disease within 2 years. A history of primary immunodeficiency is known. Patients with only positive autoantibodies will be asked to confirm the presence of autoimmune disease at the discretion of the investig
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| relapse free survival, RFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival, OS;Proportion of progression before surgery;Rate of a 6-week delay in surgery due to receipt of neoadjuvant therapy;Incidence of microvascular invasion and satellite lesions; | — |
Countries
China
Contacts
Public ContactZhe Liu
Faculty of Hepato-Pancreato-Biliary Surgery,the first medical center of Chinese PLA general
Outcome results
None listed