HAIC Combined With Bevacizumab and Toripalimab for Advanced Hepatocellular Carcinama

HAIC Synchronously Combined With Bevacizumab and Toripalimab First-line for Advanced Hepatocellular Carcinama

This is an open-label, single-arm clinical study to preliminarily observe and evaluate the efficacy and safety of hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin synchronous combined with Bevacizumab and Toripalimab as the first-line therapy for advanced HCC.

Hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, 5-fluorouracil and leucovorin was effective and safe for hepatocellular carcinoma. Bevacizumab, an angiogenesis Inhibitors was effectively used for hepatocelluar carcinama (HCC) therapy. Toripalimab, an programmed cell death protein-1 (PD-1) antibody, was effective and tolerable in patients with hepatocellular carcinoma and portal vein tumor thrombus. No study has evaluated HAIC plus Bevacizumab and Toripalimab. Thus, the investigators carried out this prospective, single-arm study to find out it.

Inclusion Criteria:

1. HCC diagnosed by histopathological examination or Guidelines for Diagnosis and Treatment of Primary Liver Cancer or the recurrent HCC after surgery;
2. age between 18 and 75 years;
3. Stage B (middle stage) or C (late stage) HCC determined in accordance with Barcelona Clinic Liver Cancer staging system (BCLC stage). In case of stage B.
4. No previous use of any systemic therapy or recurrent HCC.
5. Child-Pugh class A or B;
6. Eastern Cooperative Group performance status (ECOG) score of 0-2;
7. Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 30mmol/L Serum albumin ≥ 32 g/L ASL and AST ≤ 5 x upper limit of normal Serum creatinine ≤ 1.5 x upper limit of normal INR ≤ 1.5 or PT/APTT within normal limits Absolute neutrophil count (ANC) >1,500/mm3
8. Prothrombin time ≤18s or international normalized ratio < 1.7.
9. Ability to understand the protocol and to agree to and sign a written informed consent document.

Exclusion Criteria:

1. Cholangiocellular carcinoma (ICC);
2. Patients with cancer thrombus in the main trunk of portal vein (Vp4), or cancer thrombus in inferior vena cava should be excluded;
3. Accepting ablation or surgery or other system therapy as firt line therapy after diagnose for primary HCC, ablation or system therapy as first line therapy for recurrent HCC.
4. Serious medical comorbidities.
5. Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy
6. Known history of HIV
7. History of organ allograft
8. Known or suspected allergy to the investigational agents or any agent given in association with this trial.
9. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
10. Evidence of bleeding diathesis.
11. Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.