A Trial of Hepatic Arterial Infusion Combined With Apatinib and Camrelizumab for C-staged Hepatocellular Carcinoma in BCLC Classification

Inclusion Criteria:

1. The patient voluntarily joins the study and signs an informed consent;
2. Age ≥ 18 years old, ≤ 70 years old, both men and women;
3. Clinical or pathologically confirmed BCLC C-stage hepatocellular carcinoma, no furtherfirst-line treatment;
4. At least one intrahepatic evaluable tumor existed, intrahepatic tumor is the primarytumor burden;
5. Child-Pugh score small or equal to 7 points (Child-Pugh A-B);
6. The liver tumor burden does not exceed 50% of the total liver volume;
7. Patient can swallow tablet normally;
8. ECOG score: 0 to 1 (according to the ECOG score classification);
9. The expected survival is longer than 12 weeks;
10. The laboratory parameters meets the following requirements (no blood components andcell growth factors are allowed within 14 days before the first dose):

• Absolute neutrophil count ≥ 3.0 × 109 / L;
• Platelets ≥ 80 × 109 / L;
• Hemoglobin ≥ 90 g / L;
• serum albumin ≥ 28 g / L;
• Thyroid stimulating hormone (TSH) ≤ 1 × ULN (if abnormalities should beconsidered at the same time FT3, FT4 levels, patients with FT3 and FT4 levels innormal range can also be enrolled);
• bilirubin ≤ 1.5 × ULN (within 7 days prior to the first dose);
• ALT ≤ 3 x ULN and AST ≤ 3 x ULN (within 7 days prior to the first dose);
• AKP ≤ 2.5 × ULN; serum creatinine ≤ 1.5 × ULN;

11. For female that non-surgical sterilization or in childbearing age need to use amedically approved contraceptive (such as an intrauterine device, contraceptive orcondom) during the study period and within 3 months after the end of the studytreatment period; For female that non-surgical sterilization or in childbearing agemust have a negative serum or urine HCG test within 72 hours prior to studyenrollment; and must be non-lactating; for male patients whose partner in achildbearing age, effective methods of contraception should be given during the trialand at the end of Camrelizumab injection.

Exclusion Criteria:

1. The patient has any active auto-immune disease or a history of auto-immune disease (such as the following, but not limited to: auto-immune hepatitis, interstitialpneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis,nephritis, thyroid hyperfunction; patients with vitiligo. For patient with history ofasthma, complete remission of asthma in childhood without any intervention afteradulthood can be included, while those asthma patients who require bronchodilators formedical intervention cannot be included.);
2. The patient is using immunosuppressive agents or systemic hormonal therapy forimmunosuppression purposes (dose > 10 mg/day of prednisone or other therapeutichormones) and continues to be used within 2 weeks prior to enrollment;
3. Severe allergic reactions to other monoclonal antibodies;
4. Known for a history of central nervous system metastasis or hepatic encephalopathy;
5. Having a history of organ transplantation;
6. Patients with clinically symptomatic ascites who require puncture, drainage, orascites drainage within 3 months, except for those who have a small amount of ascitesbut no clinical symptoms;
7. Suffering from hypertension, and cannot be well controlled by antihypertensive drugs (systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥90 mmHg);
8. Suffering heart diseases with clinical symptoms or those not well controlled, such as: (1) heart failure in NYHA class 2 or higher; (2) unstable angina; (3) myocardialinfarction occurred within 1 year; (4) clinically symptomatic supraventricular orventricular arrhythmia requiring treatment or intervention; (5) Tc > 450ms (male); QTc > 470ms (female);
9. Coagulation dysfunction (INR>2.0, PT>16s), bleeding tendency or receiving thrombolysisor anticoagulant therapy, allowing prophylactic use of low-dose aspirin or lowmolecular heparin;
10. There are significant clinically significant bleeding symptoms or clear bleedingtendency within 3 months before enrollment, such as hemoptysis of 2.5ml or more perday, gastrointestinal bleeding, esophageal varices with bleeding risk, hemorrhagicgastric ulcer or vasculitis, etc. If the fecal occult blood is positive in thebaseline period, it can be watched, then gastroscope is needed for those fecal occultblood is still positive. If the gastroscope indicates severe esophageal varices, itcannot be enrolled, except for those who have undergone gastroscopy within a month orless to exclude such cases);
11. Events of arterial/venous thrombosis occurring within the first 6 months ofenrollment, such as cerebrovascular accidents (including transient ischemic attacks,cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonaryembolism;
12. There are known hereditary or acquired bleeding and thrombophilia (such as hemophiliapatients, coagulopathy, thrombocytopenia, etc.);
13. Urine routine indicates that urine protein ≥ ++ and 24-hour urine protein amount > 1.0g was confirmed;
14. The patient has active infection, unexplained fever (≥38.5 °C) within 3 days beforeadministration, or baseline white blood cell count>15×109/L; 15 Patients withcongenital or acquired immunodeficiency (such as HIV-infected patients);
15. HBV-DNA>2000 IU/ml (or 104 copies/ml); or HCV-RNA>103 copies/ml; or HBsAg+ and anti-HCVantibody positive patients; 17. The patient has had other malignant tumors in the past 3years or at the same time (except for cured skin basal cell carcinoma and cervicalcarcinoma in situ); 18. Patients with bone metastases who had received palliativeradiotherapy >4% of the bone marrow area within 4 weeks prior to participation in thestudy; 19. Patients have previously received other anti-PD-1 antibody therapy or otherimmunotherapy against PD-1/PD-L1, or have received apatinib before; 20. Inoculation of alive vaccine within less than 4 weeks prior to study or possibly during the study period;
16. Pregnant or lactating women, or women of childbearing age who are unwilling to takecontraceptive measures; 22. According to the investigators, the patient has other factorsthat may affect the results of the study or lead to the termination of the study, such asalcohol abuse, drug abuse, other serious diseases (including mental illness) requiringcombined treatment, and serious laboratory tests, abnormalities, accompanied by factorssuch as family or society, which may affect the safety of enrolled patients.