Hepatocellular carcinoma
Conditions
Interventions
Neoadjuvant Therapy group:Patients in this group receive preoperative TACE combined with lenvatinib and sintilimab for 1–N treatment cycles. The first TACE procedure is completed within one week after
Control group:Radical surgery + sintilimab + lenvatinib 4 weeks after surgery for half a year.
Sponsors
The Third Affiliated Hospital of Naval Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Subjects were required to meet the following eligibility criteria: 1. Written informed consent was obtained before any trial-related procedures were performed; 2. Age 18-75 years old, male or female; 3. ECOG PS score of 0-1; 4. Hepatocellular carcinoma confirmed by pathology or imaging; 5. Single tumor with a maximum diameter of more than 5cm; 6. The imaging evaluation was resectable and there was sufficient remnant liver volume after hepatectomy; 7. There was no vascular invasion or extrahepatic metastasis. 8. Had received no previous local or systemic antitumor therapy for hepatocellular carcinoma; 9. Child-Pugh grade A; 10. Expected survival time >12 months; 11. Total triiodothyronine (T3) or free T3 and free thyroxine (T4) are within normal limits. (It can be controlled with thyroid replacement therapy). Asymptomatic subjects with abnormal T3, free T3 or free T4 were eligible; 12. Adequate blood pressure control; 13. Adequate organ and bone marrow function with laboratory values within 7 days before randomization (administration of any blood component, cell growth factor, albumin, or other corrective medication was not allowed within 14 days of obtaining the laboratory test), as follows: 1) Blood routine: absolute neutrophil count (ANC) >=1.5×109/L; platelet count (PLT) >=75×10 9/L; hemoglobin (HGB) >=9.0 g/dL; 2) Liver function: serum total bilirubin (TBIL) =30g/L; 3) Renal function: serum creatinine (Cr) = 50mL/min (Cockcroft-Gault formula); Urine routine results showed that urine protein was less than 2+. Patients with a urine protein level of 2+ or more on routine urinalysis at baseline should undergo 24-hour urine collection with a 24-hour urinary protein quantification of less than 1g. 4) Coagulation: international normalized ratio (INR) and activated partial thromboplastin time (APTT) <= 1.5 times ULN; 14. If you have hepatitis B virus (HBV) infection, if you are HBsAg positive, you need to test for HBV-DNA, and HBV-DNA should be <2000 IU/mL (<104 copy/mL if the research center has only copy/mL testing unit). Patients who had received anti-HBV treatment for at least 1 week before randomization and were willing to receive antiviral treatment for the whole period of the study; Hepatitis C virus (HCV) -RNA-positive patients must receive antiviral therapy according to the treatment guidelines. 15. For women of childbearing age, a negative urine or serum pregnancy test should be performed within 3 days prior to receiving the first dose of study drug (day 1 of cycle 1). If a urine pregnancy test result could not be confirmed as negative, a blood pregnancy test was requested. Women who were not of reproductive age were defined as those who had been postmenopausal for at least 1 year or had undergone surgical sterilization or hysterectomy. 16. If there was a risk of pregnancy, all subjects (male or female) were required to use contraception with an annual failure rate of less than 1% for the entire treatment period up to 120 days after the last dose of study drug on treatment (or 180 days after the last dose of chemotherapy). The expected survival time was =12 weeks.
Exclusion criteria
Exclusion criteria: Subjects could not have any of the following exclusion criteria: 1. Fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma and other components previously confirmed by histology/cytology; 2. History of hepatic encephalopathy or liver transplantation; 3. Pleural effusion, ascites and pericardial effusion with clinical symptoms requiring drainage; 4. Central nervous system metastasis; 5. A bleeding event of esophageal or gastric varices due to portal hypertension within the past 6 months. Known endoscopic severe (G3) varices were present within 3 months before the first dose. Patients with evidence of portal hypertension (including splenomegaly detected by imaging examination) and high risk of bleeding as assessed by the investigator; 6. Any life-threatening bleeding event in the previous 3 months, including the need for blood transfusion, surgery or local treatment, or continuous medical treatment; 7. History of arterial or venous thromboembolic events within the previous 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other major thromboembolism. Patients with venous access port or catheter-related thrombosis or superficial venous thrombosis were excluded if the thrombosis was stable after conventional anticoagulant therapy. Prophylactic use of low-dose low-molecular-weight heparin (e.g., enoxaparin 40 mg per day) was allowed. 8. Aspirin (> 325 mg/ day) or other drugs known to inhibit platelet function, such as dipyridamole or clopidogrel, for 10 consecutive days within 2 weeks before the first dose; 9. Uncontrolled hypertension, systolic blood pressure > 150mmHg or diastolic blood pressure > 90 mmHg with best medical treatment, history of hypertensive crisis or hypertensive encephalopathy; 10. Symptomatic congestive heart failure (New York Heart Association class II-IV) Symptomatic or poorly controlled arrhythmias. A history of congenital long QT syndrome or corrected QTc > 500ms (calculated with Fridericia's method); 11. Severe bleeding tendency or coagulopathy, or receiving thrombolytic therapy; 12. History of gastrointestinal perforation and/or fistula within the previous 6 months, history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or long-term chronic diarrhea; 13. Previous or current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, severe impairment of pulmonary function and other pulmonary diseases; 14. Active pulmonary tuberculosis (TB), receiving anti-TB treatment or receiving anti-TB treatment within 1 year before the first dose; 15. Human immunodeficiency virus (HIV) infection (HIV-1/2 antibody positive), known syphilis infection; 16. Severe infections that are active or poorly controlled clinically. Severe infection within 4 weeks before the first dose, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia; 17. Active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, corticosteroids, or immunosuppressive agents) occurred within 2 years before the first dose. Alternative therapies (e.g., thyroxine, insulin, or physiologic corticosteroids for adr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Recurrence-Free Survival (RFS): Defined as the time from the date of surgery to the recurrence of the tumor.; | — |
Countries
China
Contacts
Public ContactZhou Weiping/Yang Yun
The Third Affiliated Hospital of Naval Medical University
Outcome results
None listed