HAIC Sequential TAE Combined With Lenvatinib and Tislelizumab in Unresectable HCC (FRONT-1)

This is an interventional treatment trial for Liver Cancer focused on measuring hepatocellular carcinoma, hepatic arterial infusion chemotherapy, lenvatinib, tislelizumab Read More

Inclusion Criteria:

• HCC is diagnosed in accordance with the clinical diagnostic criteria of the Guidelines for the Diagnosis and Treatment of primary liver Cancer (2019 edition) issued by the Health Commission of the People's Republic of China or by histopathology;
• ECOG PS 0 or 1;
• Child-Pugh A liver function;
• Chinese Liver Cancer (CNLC) stage IIb, IIIa and IIIb patients, or CNLC stage Ib and IIA patients who cannot undergo hepatectomy for various reasons;
• Expected survival time ≥6 months;
• HCC patients with incomplete portal vein obstruction or complete portal vein obstruction with abundant compensatory collateral vessels;
• Hematological indicators should meet the following conditions: hemoglobin ≥90 g/L; absolute neutrophil count ≥1.5×10^9/L; platelets ≥80×10^9/L; total bilirubin ≤1.5×ULN; ALT 3 x ULN or less; AST 3 x ULN or less; alkaline phosphatase ≤2.5×ULN; serum albumin ≥28 g/L; serum creatinine ≤1.5×ULN;
• Urinary protein <2+ or 24 h urinary protein < 1.0 g;
• For women of reproductive age, use of contraception (e.g. intrauterine devices, tablets or condoms) is required during the course of the clinical trial until 120 days after the end of the clinical trial; Women of childbearing age had negative serum or urine HCG test results within 7 days before enrollment in the study; male patients with potential reproductive partners should use effective contraception during the study period and for 120 days after the study.

Exclusion Criteria:

• Previous or co-existing other malignancies except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix;
• Previously received HAIC, TACE, TAE, radiofrequency ablation and other local treatments for HCC;
• Patients who have received or are using one of the following three drugs in the previous 6 months: ① immune checkpoint inhibitors, including but not limited to artemizumab, nivolumab, pembrolizumab, camrelizumab, sintilimab, toripalimab, and tislelizumab; ② molecular targeted therapy, including but not limited to sorafenib, lenvatinib, apatinib, regorafenib, anlotinib, bevacizumab, etc. ③ systemic chemotherapy drugs (such as doxorubicin, oxaliplatin, 5-FU, S-1, etc.);
• Having a congenital or acquired immunodeficiency disease (e.g. being HIV positive);
• Active infection, or body temperature ≥ 38.5℃ or white blood cell count > 15 x 10^9/L 7 days before enrollment;
• Within 3 months of enrollment, patients with hemorrhagic diseases (including but not limited to moderate/severe esophageal and gastric variceal bleeding, gastrointestinal bleeding, hemorrhagic gastric ulcer, hemoptysis > 2.5 mL per day; For positive cases of fecal occult blood, occult blood should be reexamined, and gastroenteroscopy should be performed if necessary);
• Arterial or venous thrombosis within 6 months, such as cerebrovascular accident (transient ischemic attack, cerebral hemorrhage, cerebral infarction, etc.), deep vein thrombosis, pulmonary infarction, etc.;
• Those who have a history of alcohol or psychotropic drug abuse and are unable to abstain or have mental disorders;
• Pregnant or lactating women;
• Active autoimmune diseases or previous autoimmune diseases (such as autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, etc.);
• Being treated with immunosuppressive agents or glucocorticoids (>10mg prednisone/day) within 2 weeks;
• Complicated with hepatic encephalopathy or brain metastasis;
• Medically uncontrolled hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg) (based on the average of BP readings obtained from ≥2 measurements);
• Uncontrolled heart disease or symptoms (including but not limited to cardiac function grade II or above, unstable angina pectoris, myocardial infarction in the previous 1 year, supraventricular or ventricular arrhythmias requiring treatment or intervention);
• Abnormal coagulation (INR > 2.0, PT > 16 s), bleeding tendency or need for thrombolytic therapy or anticoagulant therapy (although prophylactic use of low-dose aspirin or low molecular weight heparin is permitted);
• Hereditary or acquired blood diseases (e.g. hemophilia, thrombocytopenia, coagulopathy, etc.);
• Urinary protein ≥ ++ and 24-hour urinary protein 1.0 g in urine routine;
• Patients with bone metastases requiring surgical treatment for bone metastases;
• Known hypersensitivity to active ingredients or excipients contained in the study drugs (tislelizumab, lenvatinib), or a history of severe allergy to any other monoclonal antibody or antiangiogenic targeted drug.