Observational Study of Factors Predicting Therapeutic Effects and Clinical Prognosis After HAIC for Locally Advanced HCC

Inclusion Criteria:

• Written informed consent must be obtained prior to any screening procedures.
• Cytohistological confirmation is required for diagnosis of HCC.
• Patients with advanced (unresectable and/or metastatic, stage C based onBarcelona-Clinic Liver Cancer [BCLC] staging classification) hepatocellular carcinomawhich would not be suitable for treatment with loco-regional therapies or haveprogressed following locoregional therapy such as surgical resection, percutaneoushepatic arterial embolization, radiofrequency ablation, and percutaneousinterventional therapy.
• At least one tumor lesion meeting measurable disease criteria as determined by RECISTv1.1. Lesions previously treated with local therapy, such as radiation therapy,hepatic arterial embolization, radiofrequency ablation, and percutaneousinterventional therapy should not be selected unless progression is noted at baseline,in which case, these lesions would be considered as non-target lesions.
• Current cirrhotic status of Child-Pugh class A-B, with no encephalopathy. Ascitescontrolled by diuretics is permitted in this study.
• Availability of a representative tumor tissue specimen (archival tumor tissue isallowed) at pre-screening.
• Eastern Cooperative Oncology Group Scale for Assessment of Patient Performance Status ≤ 2.
• Both men and women enrolled in this trial must use adequate barrier birth controlmeasures during the course of the trial and 4 weeks after the completion of trial.
• Adequate bone marrow, liver and renal function as assessed by central lab by means ofthe following laboratory requirements from samples within 7 days prior to procedure:
• Hemoglobin > 100g/L
• Absolute neutrophil count >3.0 ×109/L
• Neutrophil count > 1.5 ×109/L
• Platelet count ≥ 50.0 ×109/L
• Total bilirubin < 51 μmol/L
• Alanine transaminase (ALT) and aminotransferase (AST) < 5 x upper limit of normal
• Albumin > 28 g/L
• Prothrombin time (PT)-international normalized ratio (INR) < 2.3, or PT < 6 secondsabove control
• Serum creatinine < 110 μmol/L
• Willing and able to comply with scheduled visits, treatment plan and laboratory tests.

Exclusion Criteria:

• Received any prior systemic chemotherapy or molecular-targeted therapy for HCC such assorafenib, lenvatinib.
• Previous local therapy completed less than 4 weeks prior to the dosing and, if presentany related acute toxicity > grade 1.
• Any contraindications for hepatic arterial infusion procedure:
• Impaired clotting test (platelet count < 60000/mm3, prothrombin activity < 50%).
• Renal failure / insufficiency requiring hemo-or peritoneal dialysis.
• Known severe atheromatosis.
• Known uncontrolled blood hypertension (> 160/100 mm/Hg).
• Patients with any other malignancies within the last 3 years before study start.
• History of HCC tumor rupture.
• Patients with severe encephalopathy.
• Patients with known active bleeding (e.g. from GI ulcers, esophageal varices) within 2months prior to baseline/screening visit or with history or evidence of inheritedbleeding diathesis or coagulopathy.
• Clinically significant (CTC grade 3 or 4) venous or arterial thrombotic disease withinpast 6 months.
• History of cardiac disease:
• Congestive heart failure >New York Heart Association (NYHA) class 2 (refer to Appendix 13.9).
• Active coronary artery disease (CAD) (myocardial infarction more than 6 months priorto study entry is allowed).
• Cardiac arrhythmias (>Grade 2 NCI-CTCAE Version 4.0) which are poorly controlled withanti-arrhythmic therapy or requiring pace maker.
• Uncontrolled blood hypertension (> 160/100 mm/Hg).
• Serious, non-healing wound, ulcer, or bone fracture.
• History of abdominal fistula, GI perforation, or intra-abdominal abscess within past 6months prior to study treatment.
• Clinically significant third space fluid accumulation (i.e., ascites requiring tappingdespite use of diuretic or pleural effusion that either required tapping or isassociated with shortness of breath).
• Patients who have undergone major surgical procedure, open biopsy, or significanttraumatic injury within 4 weeks of the start of protocol treatment.
• History of a bone marrow or solid organ transplant.
• Use of biologic response modifiers, such as G-colony stimulating factor (CSF), within 3 weeks prior to start of study drug. (G-CSF and other hematopoietic growth factorsmay be used in the management of acute toxicity such as febrile neutropenia whenclinically indicated or at the discretion of the investigator; however, they may notbe substituted for a required dose reduction). Subjects taking chronic erythropoietinare permitted provided no dose adjustment is undertaken within 1 month prior to thestudy or during the study.
• Any other condition that would, in the Investigator's judgment, contraindicatepatient's participation in the clinical study due to safety concerns or compliancewith clinical study procedures, e.g., infection/inflammation, intestinal obstruction,unable or unwilling to swallow medication, social/ psychological issues, etc.
• Unable to undergo either contrast-enhanced magnetic resonance imaging (MRI) orcontrast-enhanced computed tomography (CT).
• Known history of human immunodeficiency virus (HIV) seropositivity. HIV testing is notrequired as part of this study.
• Patients who have received any other investigational agents within a period of timethat is less than the cycle length used for that treatment or equal to 4 weeks (whichever is shorter) prior to starting study drug and recovered from any sideeffects to grade 1 or less.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of afemale after conception and until the termination of gestation, confirmed by apositive human chorionic gonadotropin (hCG) laboratory test.