Phase II Study of Fruquintinib Combined With Sintilimab and TACE for Inoperable Primary Hepatocellular Carcinoma

Inclusion Criteria:

1. Age 18-75 years, male or female;
2. Patients diagnosed with primary hepatocellular carcinoma (HCC) based on clinical diagnosis or pathology;
3. Patients diagnosed with Chinese stage IIb-IIIa according to the Primary Liver Cancer Diagnostic and Treatment Protocol (2019 version), and evaluated by the investigator to be unable to undergo surgical treatment, such as resection, ablation or liver transplantation;
4. Imaging reports within 14 days prior to the intervention showed the presence of at least 1 target lesion measurable by CT or MRI, and the lesion is suitable for repeated accurate measurements;
5. Child-Pugh liver function rating: grade A or better B (≤7 points);
6. ECOG score: 0-1;
7. all lesions amenable to phase 1 or 2 (fractionated TACE) TACE therapy;
8. Good organ and bone marrow function. Blood count: WBC\>4. 0 × 109/L, Hb\>80g/L, PLT\>75 ×109/L, NEUT\>/ 1.5 × 109/L; coagulation function:International normalized (prothrombin time) ratio(INR) \<1.2; liver function indexes: serum albumin (ALB) \>3.5 g/dl, serum total bilirubin(TBIL) \<1.5 times the upper limit of normal value (excluding biliary obstruction), serum transaminases (ALT and AST)\<3 times the upper limit of normal value; renal function: serum myelin (CR) \<1.5 times the upper limit of normal value;
9. Patients with positive hepatitis B surface antigen need to have received anti-hepatitis B treatment prior to inclusion in the study;
10. Signed an informed consent form, were compliant and cooperated with the follow-up.

Exclusion Criteria:

1. Hepatobiliary cell carcinoma, sarcomatoid hepatocellular carcinoma, mixed cell carcinoma and fibrous lamellar hepatocellular carcinoma;
2. With portal trunk or vena cava invasion;
3. Having received interventional treatment such as TACE within 2 years
4. Combined with medical contraindications that preclude any contrast-enhanced imaging (CT or MRI);
5. Previous systemic therapy;
6. Uncontrollable ascites, hepatic encephalopathy or bleeding esophagogastric fundic varices;
7. Hypertension that cannot be reduced to within normal limits with antihypertensive medication (systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg);
8. Suffering from myocardial ischemia or myocardial infarction of grade II or higher, poorly controlled arrhythmia of grade II or higher myocardial ischemia or infarction, poorly controlled arrhythmia (QTc interval greater than or equal to 450 ms, QTc interval calculated in Fridericia metric).

   (calculated in Fridericia formula);
9. History of gastrointestinal bleeding within the past 3 months or a clear tendency of gastrointestinal bleeding, such as: esophageal varices at risk of bleeding, locally active ulcer lesions, fecal occult blood (++);
10. Pregnant or breastfeeding women; patients of childbearing potential who are unwilling or unable to use effective contraceptive measures
11. HIV-infected patients;
12. Those suspected of being allergic to the study drug;
13. Other circumstances that, in the judgment of the investigator, may affect the conduct of the clinical study and the determination of the study results.