Hepatic Artery Infusion Chemotherapy for Unresectable Hepatocelluar Carcinoma Who Failed to Systemic Therapy

Inclusion Criteria:

• Hepatocellular carcinoma diagnosed histologically/cytologically, or meeting theclinical diagnostic criteria of the "Guidelines for the Diagnosis and Treatment ofHepatocellular Carcinoma (2019 Edition)."
• Unresectable or advanced hepatocellular carcinoma that was assessed by theinvestigator. Advanced hepatocellular carcinoma was defined as BCLC C stage or ChineseLiver Cancer stage (CNLC) IIIa or IIIb stage.
• Had at least one measurable lesion in the liver.
• Liver function Child-Pugh classification of A or B7.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Patients who have received combination therapy with targeted agents combined withimmune checkpoint inhibitors and have developed intolerable adverse effects or imagingconfirmed intrahepatic tumor progression and have signed an informed consent form.Targeted agents include sorafenib, lenvatinib, donafenib, regorafenib, apatinib,bevacizumab (or biosimilar), and anlotinib; immune checkpoint inhibitors (mainlyPD-1/PD-L1 antibodies) include pembrolizumab, nivolumab, camrelizumab, sintilimab,toripalimab, atezolizumab, and tislelizumab. Additional eligible subjects: subjectswho have received at least one HAIC treatment were entered into safety evaluation (SAS); subjects who have received at least one imaging evaluation after treatment wereentered into effectiveness evaluation (ITT).
• Adequate bone marrow and organ function. Reassessment of bone marrow and organfunction as described above is required prior to each HAIC treatment.
• Leukocytes ≥ 3 x 10^9/L within the last 14 days.
• Platelets ≥ 50×10^9/L in the last 14 days without transfusion.
• hemoglobin ≥ 90 g/L in the last 14 days without blood transfusion orerythropoietin administration.
• total bilirubin ≤ 2 x the upper limit of normal (ULN)
• albumin ≥ 30 g/L in the absence of human albumin or plasma transfusion within thelast 14 days
• AST and ALT ≤ 3 x ULN.
• serum creatinine at ≤1.5×ULN.
• International Normalized Ratio (INR) of prothrombin time ≤ 1.5×ULN.
• Serum HBV DNA < 2 x 10^3 IU/mL; for HBV DNA > 2 x 10^3 IU/mL, treatment withnucleoside analogs for at least 1 week.
• Without grade 3 or higher adverse events (NCI CTCAE 4.0 criteria) induced by previoussystemic therapy, or grade 3 or higher events reactions have recovered to grade 2 orlower.

Exclusion Criteria:

• Pathologic diagnosed with mixed liver cancer, fibrous lamellar cell carcinoma or othernon-hepatocellular malignancy component.
• Previous or concurrent other malignancies, except adequately treated non-melanoticskin cancer, carcinoma in situ of the cervix, and papillary thyroid cancer
• History of organ transplantation or hepatic encephalopathy.
• Hypersensitivity to iodine-containing contrast agents, oxaliplatin, calcium folinicacid, and fluorouracil.
• History of gastrointestinal perforation and/or fistula within 6 months, history ofintestinal obstruction (including incomplete intestinal obstruction requiringparenteral nutrition), extensive bowel resection (partial colectomy or extensive smallbowel resection complicated by chronic diarrhea), Crohn's disease, ulcerative colitis,or long-term chronic diarrhea.
• Uncontrollable hypertension, systolic blood pressure > 140 mmHg or diastolic bloodpressure > 90 mmHg after optimal medical therapy, history of hypertensive crisis orhypertensive encephalopathy.
• Gastrointestinal bleeding due to portal hypertension within 6 months; G3 varices bygastrointestinal endoscopy within 3 months.
• Subjects requesting withdrawal of informed consent.
• Other circumstances that the investigator deems inappropriate for participation in theclinical trial.