explore the effectiveness and safety of conventional transarterial chemoembolization (cTACE) or transarterial chemoembolization (DEB-TACE) plus hepatic arterial Infusion chemotherapy (HAIC) combined with regorafenib and anti-PD-1 antibody or not for unresected hepatocellular carcinoma (uHCC)

This is a non-randomized, open, single-arm clinical study. Patients receive cTACE/DEB-TACE+HAIC treatment( 6-8 weeks as a cycle) and regorafenib and anti-PD1 antibody or not until the disease progresses, intolerable toxicity occurs, the patient is lost to follow-up or death, or situations other judged by researchers which treatment should be stopped.

Inclusion Criteria:

1. Volunteer to participate and sign the informed consent in writing;
2. Age: 18-75 years old;
3. No gender limit;
4. Unresectable hepatocellular carcinoma with clear pathological diagnosis or clinical diagnosis;
5. Unresectable hepatocellular carcinoma patients who failed first-line treatment (including but not limited to sorafenib, lenvatinib, atezolizumab combined with bevacizumab, etc.);
6. At least one measurable lesion (according to mRECIST criteria) imaging diagnosis time ≤ 21 days from selection;
7. Child-pugh grade A-B7 grade
8. The expected survival period is ≥3 months;
9. General physical condition (ECOG) 0-2;
10. Sufficient bone marrow hematopoietic function (within 7 days): hemoglobin ≥9 g/dL, white blood cells ≥3.0×10^9/L, neutrophils ≥1.5x 10^9/L, platelets ≥80x 10^9/L; liver and kidney functions are normal; (Within 14 days): TBIL≤1.5 times the upper limit of normal; ALT and AST≤5 times the upper limit of normal; creatinine≤1.5 times the upper limit of normal; INR≤1.7 or prolonged PT≤4s.

Exclusion Criteria:

1. Those who are currently receiving other effective treatments;
2. Patients who have received regorafenib in the past;
3. Patients who have participated in other clinical trials within 4 weeks before enrollment;
4. Unable to cooperate with cTACE and HAIC treatment;
5. Patients with primary malignant tumors other than hepatocellular carcinoma at the same time, except for cured skin basal cell carcinoma and cervical carcinoma in situ;
6. Clinically significant cardiovascular diseases, such as heart failure (NYHA III-IV), uncontrolled coronary heart disease, cardiomyopathy, arrhythmia, uncontrolled hypertension or a history of myocardial infarction within the past 1 year;
7. Neurological or mental abnormalities that affect cognitive ability, including central nervous system transfer;
8. There were active serious clinical infections (>grade 2 NCI-CTCAE version 4.0), including active tuberculosis within 14 days before enrollment;
9. Known or self-reported HIV infection;
10. Uncontrolled systemic diseases, such as poorly controlled diabetes;
11. Known to have hypersensitivity or allergic reactions to any component of the study drug;
12. Pregnancy (determined by serum β-chorionic gonadotropin test) or breast-feeding

patients with unresectable hepatocellular carcinoma are fail for fisrt line treatment((including but not limited to sorafenib, levatinib, atelizumab combined with bevacizumab, etc.) and will received cTACE/DEB-TACE plus HAIC and regorafenib and anti-PD1 antibody or not.