Overview

Although resection provided survival benefit for selected HCC patients with PVTT, the recurrence rate is still high for those patients. It is still unknown whether perioperative Sintilimab, a PD-1antibody, plus bevacizumab biosimilar and TACE-HAIC will improve the survival for those patients. We initialed this phase 2 clinical trial to prove the perioperative therapy.

Eligibility

Inclusion Criteria:

• Clinically diagnosed or pathologically confirmed advanced hepatocellular carcinoma (unresectable or metastatic), at least one measurable focus without local treatment (according to mRECIST requirements, the measurable focus spiral CT scan length ≥ 10 mm or enlargement Short diameter of lymph node ≥15 mm); Child-Pugh score ≤ 6 points (Child-Pugh A); BCLC staging is stage C; PVTT classification is combined with PVTT (program classification PVTT ≤ 3), and a single lesion in the liver (or multiple lesions with diameter) ≤ 7cm of primary liver cancer.

        Newly diagnosed patients who have not received targeted therapy or immunotherapy in the
        past; ECOG score: 0～1 (see Annex 1 for ECOG scoring criteria); Expected survival period ≥
        12 weeks;
        The functions of vital organs meet the following requirements (no blood components, cell
        growth factors and other corrective treatment drugs are allowed within 14 days before the
        first administration):
        Exclusion Criteria:
          -  The patient has any active autoimmune disease or a history of autoimmune disease; The
             patient is using immunosuppressive agents or systemic hormone therapy to achieve the
             purpose of immunosuppression (dose>10mg/day prednisone or other curative hormones),
             and continues to use it within 2 weeks before enrollment; The number of system
             treatment lines ≥ 2 lines; Severe allergic reaction to other monoclonal antibodies;
             Those with a known history of central nervous system metastasis or hepatic
             encephalopathy; Patients whose liver tumor burden is greater than 50% of the total
             liver volume, or who have received liver transplantation in the past; Ascites with
             clinical symptoms, those who need puncture, drainage, or those who have received
             ascites drainage within the past 3 months, except those who have only a small amount
             of ascites on imaging but not accompanied by clinical symptoms; Suffer from high blood
             pressure and cannot be well controlled by antihypertensive drugs (systolic blood
             pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg); Uncontrolled cardiac
             clinical symptoms or diseases, such as: NYHA level 2 or higher heart failure, unstable
             angina pectoris, myocardial infarction occurred within 1 year, clinically significant
             supraventricular or ventricular arrhythmia requires treatment or intervention ,
             QTc>450ms (male); QTc>470ms (female); Abnormal coagulation function (INR>2.0, PT>16s),
             have bleeding tendency or are receiving thrombolysis or anticoagulation therapy, and
             allow the preventive use of low-dose aspirin and low molecular heparin; Significant
             clinically significant bleeding symptoms or clear bleeding tendency occurred within 3
             months before randomization, such as pertussis/hemoptysis 2.5ml or more,
             gastrointestinal bleeding, esophageal and gastric varices with bleeding risk,
             hemorrhagic stomach Ulcer or vasculitis, etc., if the stool occult blood is positive
             at the baseline, it can be re-examined. If it is still positive after the
             re-examination, a gastroscopy is required. If the gastroscope shows severe esophageal
             and gastric varices, it cannot be included in the group (3 before the group) Except
             those who have undergone gastroscopy within a month or less to exclude such cases);
             Arterial/venous thrombosis events that occurred within 6 months before randomization,
             such as cerebrovascular accidents (including temporary ischemic attacks, cerebral
             hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism; Known
             genetic or acquired bleeding and thrombotic tendency (such as hemophilia patients,
             coagulation dysfunction, thrombocytopenia, etc.); Urine routine test showed urine
             protein ≥ ++ and confirmed 24-hour urine protein content> 1.0 g; Patients who have
             previously received radiotherapy, chemotherapy, hormone therapy, and surgery, after
             the completion of the treatment (last medication) and less than 4 weeks before the
             study medication; molecular targeted therapy (including other oral targeted drugs used
             in clinical trials) is less than the first study medication <5 drug half-lives, or
             patients whose adverse events (except alopecia) caused by previous treatment have not
             recovered to ≤ CTCAE level 1;
        The patient suffered from other malignant tumors in the past 3 years or at the same time
        (except for cured skin basal cell carcinoma and cervical carcinoma in situ); Patients with
        bone metastases who received palliative radiotherapy within 4 weeks before participating in
        the study >5% of the bone marrow area; The patient has previously received other anti-PD-1
        antibody therapy or other immunotherapy against PD-1/PD-L1, or has previously received
        apatinib therapy; Live vaccine may be vaccinated less than 4 weeks before study medication
        or may be administered during the study period; According to the judgment of the
        investigator, the patient has other factors that may affect the results of the study or
        cause the study to be terminated halfway, such as alcoholism, drug abuse, other serious
        diseases (including mental illness) that require combined treatment, and serious laboratory
        tests