Hepatocellular Carcinoma, HCC
Conditions
Interventions
Neo-adjuvant group:Preoperative neoadjuvant therapy with sindilizumab combined with bevacizumab
Sponsors
The First Affiliated Hospital of Guangxi Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Participate in this study voluntarily, sign the informed consent form (ICF), have good compliance, and cooperate with follow-up; Age 18-75 years old, male or female; Hepatocellular carcinoma confirmed by histopathology, cytology or imaging; Patients with stage ?a~?a hepatocellular carcinoma of CNLC deemed operable by a group discussion of liver surgery experts; Has not received systematic therapy for hepatocellular carcinoma, including chemotherapy, targeted therapy, immunotherapy, etc.; Patients who had previously received radical surgery or radical ablation were allowed to enroll, except those who had relapsed within 2 years after radical surgery and those who had previously received other local treatments. At least one measurable lesion according to RECIST V1.1; Child-Pugh liver function rating: Grade A (=6 points); ECOG PS score: 0~1; Expected survival = 12 weeks; For hepatitis B virus (HBV) infection: HBsAg positive, HBV-DNA testing < 2000 IU/mL or 104 copies /ml), receiving anti-HBV therapy for at least 1 week prior to randomization and willing to receive antiviral therapy throughout the study period: Hepatitis C virus (HCV) -RNA-positive patients (RNA < 103 copies /ml) must receive antiviral therapy according to treatment guidelines; Has adequate organ and bone marrow function, laboratory test values within 7 days prior to enrollment meet the following requirements (no blood components, cell growth factors, albumin, or other corrective drugs are allowed within 14 days prior to laboratory test), as follows: 1) Blood routine: absolute neutrophil count (ANC) =1.5×109/L; platelet count (PLT) =75×109/L; hemoglobin content (HGB) =9.0 g/dL. 2) Liver function: serum total bilirubin (TBIL) =2× upper limit of normal value (ULN); alanine aminotransferase (ALT) and aspartate transferase (AST) =5×ULN; Serum albumin =28 g/L; alkaline phosphatase (ALP) =5×ULN. 3) Renal function: serum creatinine (Cr) =1.5×ULN or clearance of creatinine (CCr) =50mL/min(Cockcroft-Gault formula); Urine routine results showed that urine protein <2+; For patients with urine protein =2+ on routine urine tests at baseline, 24-hour urine collection and 24-hour protein quantification <1g should be performed. 4) Coagulation function: International standardized ratio (INR) and activated partial thromboplastin time (APTT) =1.5 times ULN. ; Only one of the two indicators of albumin and bilirubin in the Child-Pugh rating can be 2 points; Fertile women: must agree to abstain from sex (abstaining from heterosexual intercourse) or to use a reliable, effective method of contraception for at least 120 days from the signing of the informed consent until the final administration of the study drug. Serum HCG test must be negative within 72 hours before randomization. And must be non-lactation period; A woman is considered fertile if she has menstruated, has not yet reached postmenopausal status (no continuous periods for =12 months, no cause other than menopause is found), and has not undergone sterilization (such as hysterectomy, bilateral tubal ligation, or bilateral oophorectomy); Male subjects whose partner is a fertile woman must agree to abstain from sex or use a reliable, effective method of contraception for at least 120 days from the date of their informed consent until the final administration of the study drug. Male subjects also had to agree not to donate sperm during the same time period. Male subjects with a pregnant partner are required to us
Exclusion criteria
Exclusion criteria: Known intrahepatic cholangiocarcinoma, sarcomatoid hepatocellular carcinoma, mixed cell carcinoma (ICC more than 30%) and fibrolaminar cell carcinoma; Active malignant tumors other than HCC within 5 years or at the same time; Clinically significant bleeding symptoms or definite bleeding tendency, such as gastrointestinal bleeding, severe esophageal varicose veins, hemorrhagic ulcer or vasculitis, were found within 6 months before randomization. If stool was positive for occult blood at baseline, it could be re-examined. If stool was still positive after re-examination, gastroscopy was required. Clinically symptomatic ascites requiring therapeutic abdominal puncture or drainage, or a Child-Pugh score > 7, or a history of hepatic encephalopathy; Patients preparing for liver transplantation (other than those who have previously undergone liver transplantation); Patients with extrahepatic metastasies, severe liver function impairment (Child-Pugh grade B/C and/or ICG-R15> 20%), complicated with severe portal hypertension, complicated with severe cirrhosis, generally poor and unable to tolerate major surgery, or with serious underlying diseases unable to tolerate anesthesia; Have clinical cardiac symptoms or diseases that are not well controlled, such as: (1) Grade II or higher cardiac insufficiency according to the New York Heart Association (NYHA) (see Appendix 3) or color Doppler ultrasound electrocardiogram: LVEF (left ventricular ejection fraction) 450ms by resting electrocardiogram (male); QTc> 470ms (female); Arterial thromboembolism events, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, and cerebral infarction), deep vein thrombosis above CTCAE grade 3, pulmonary embolism, etc., had occurred within 6 months before randomization; Have high blood pressure that is not well controlled with antihypertensive medications (systolic blood pressure = 150mmHg or diastolic blood pressure = 90mmHg; Based on the average of BP readings obtained from = 2 measurements), allowing the above parameters to be achieved through the use of antihypertensive therapy; Hypertensive crisis or hypertensive encephalopathy; Received major surgery within 4 weeks prior to randomization (except for diagnosis) or expected to require major surgery during the study period; Severe, unhealed, or open wounds and active cankers or untreated fractures; Major vascular disease (e.g., aortic aneurysms requiring surgical repair or recent peripheral arterial thrombosis) within the 6 months prior to randomization; Known hereditary or acquired bleeding (e.g., coagulation disorders) or thrombotic tendencies (e.g., hemophilia, coagulation disorders, thrombocytopenia, etc.); Currently receiving full doses of oral or injectable anticoagulants or thrombolytic drugs for therapeutic purposes (allowing prophylactic use of low-dose aspirin, etc.); Aspirin (> 325 mg/ day) or other drugs known to inhibit platelet function, such as dipyridamole or clopidogrel, were used for 10 days within 2 weeks of initial administration. People with current or prior history of interstitial pneumonia or interstitial lung disease requiring hormone therapy, or other pulmonary fibrosis, institutional pneu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Major pathological remission; | — |
Secondary
| Measure | Time frame |
|---|---|
| 1 year-Event-Free Survival;pcr rates;2-year-DFS;R0 Removal rate;Overall Survival, OS;Immunologic and/or pathologic correlates of hematologic and oncologic treatment responses;Safety and tolerability;Objective Response Rate, ORR; | — |
Countries
China
Contacts
Public ContactPeng Tao
The First Affiliated Hospital of Guangxi Medical University
Outcome results
None listed