TACE Plus Camrelizumab and Apatinib for Unresectable Hepatocellular Carcinoma

Inclusion Criteria:

1. Histopathologically or clinically confirmed hepatocellular carcinoma

2. 18-80 years old.

3. Performance status (PS) ≤ 1 (ECOG scale).

4. Barcelona clinical liver cancer (BCLC) stage B or stage C.

5. Initial treatment of hepatocellular carcinoma.

6. According to mRECIST, there is at least one measurable lesion.

7. Child Pugh score ≤ 7.

8. Participant has sufficient organ and marrow functions.

9. Expected survival time ≥ 12 weeks.

10. For women of childbearing age or male patients whose sexual partners are women ofchildbearing age, effective contraceptive measures should be taken during the wholetreatment period and 6 months after the last medication.

11. Sign the written informed consent, and be able to follow the visit and relevantprocedures specified in the plan.

Exclusion Criteria:

1. Fibrolamellar carcinoma, sarcomatoid carcinoma, cholangiocarcinoma and othercomponents previously confirmed by histology / cytology.

2. History of hepatic encephalopathy or liver transplantation.

3. Pleural effusion, ascites and pericardial effusion with clinical symptoms requiringdrainage.

4. Tumor burden≥70%, diffuse liver cancer or tumor is not suitable for mRECIST standardevaluation.

5. Received local treatment (ablation therapy, TACE), surgery resection andradiotherapy for liver cancer before the first administration.

6. Have received systemic chemotherapy, targeted therapy or immunotherapy

7. There is a significant decrease in white blood cells and platelets in peripheralblood, severe coagulation dysfunction and can not be corrected：theneutrophil<1.5×109/L, PLT<50×109/L. The INR>2.3

8. Acute or chronic active hepatitis B or C infection, hepatitis B virus (HBV-DNA) > 10^6 copies / ml; hepatitis C virus (HCV-RNA) > 10^3 copies / ml; HBsAg and anti HCVantibody were positive at the same time.

9. There is central nervous system metastasis.

10. Bleeding of esophageal or gastric varices caused by portal hypertension occurred inthe past 6 months, or severe (G3) varices were found in endoscopic examinationwithin 3 months before the first administration, or evidence of portal hypertension (including splenomegaly found in imaging examination) was found. The researchersassessed that the risk of bleeding was high and did not receive sclerotherapy orligation under the endoscope.

11. The previous 6-month history of arteriovenous thromboembolism, including myocardialinfarction, unstable angina, cerebrovascular accident, pulmonary embolism, deep veinthrombosis or any other serious thromboembolism. The thrombus of implanted vein portor catheter source or superficial vein is stable after routine anticoagulanttreatment. Prophylactic use of low-molecular-weight heparin (e.g., enoxaparin 40 mg / day) is permitted.

12. Tumor thrombus of main portal vein, or involving superior mesenteric vein at thesame time.

13. Aspirin (> 325 mg / day) or other drugs known to inhibit platelet function such asdipyridamole or clopidogrel were used for 7 consecutive days within 2 weeks beforethe first administration.

14. For uncontrolled hypertension, systolic blood pressure > 150 mmHg or diastolic bloodpressure > 100 mmHg after the best medical treatment, hypertension crisis orhypertension encephalopathy history.

15. Symptomatic congestive heart failure (New York Heart Association class II-IV).Symptomatic or poorly controlled arrhythmias. The corrected QT interval (QTc) forthe history or screening of congenital long QT syndrome was more than 500 ms (calculated by Fridericia method).

16. Serious bleeding tendency or coagulation dysfunction, or undergoing thrombolysis.

17. In the past 6 months, there was a history of gastrointestinal perforation and / orfistula, a history of intestinal obstruction (including incomplete intestinalobstruction requiring parenteral nutrition), extensive enterotomy (partial colectomyor extensive enterotomy with chronic diarrhea), Crohn's disease, ulcerative colitisor long-term chronic diarrhea.

18. Previous and current pulmonary fibrosis history, interstitial pneumonia,pneumoconiosis, drug-related pneumonia, severe impairment of lung function and otherlung diseases.

19. Active tuberculosis (TB), who is receiving anti TB treatment or has received anti TBtreatment within one year before the first administration.

20. People with HIV infection (HIV 1 / 2 antibody positive) and known syphilisinfection. Serious infection in active stage or poor clinical control.

21. Severe infection within 4 weeks before the first administration, including but notlimited to hospitalization due to complications of infection, bacteremia or severepneumonia.

22. Active autoimmune diseases requiring systemic treatment (such as the use of diseasealleviation drugs, corticosteroids or immunosuppressants) occurred within 2 yearsbefore the first administration. Alternative therapies (e.g. thyroxine, insulin, orphysiological corticosteroids for adrenal or pituitary insufficiency) are permitted.Known history of primary immunodeficiency. Only the patients with positiveautoimmune antibody need to confirm whether there is autoimmune disease according tothe judgment of researchers.

23. Immunosuppressive drugs were used within 4 weeks before the first administration,excluding local glucocorticoids or systemic glucocorticoids (i.e. no more than 10 Mg / day prednisone or the equivalent dose of otherglucocorticoids), allowing temporary use of glucocorticoids due to dyspnea symptomsin the treatment of asthma, chronic obstructive pulmonary disease and otherdiseases.

24. Receive live attenuated vaccine within 4 weeks before the first administration orduring the study period.

25. Major surgical procedures (craniotomy, thoracotomy or open hand) were performedwithin 4 weeks before the first administration (surgery) or an unhealed wound,ulcer, or fracture.

26. Uncontrolled / uncorrectable metabolic disorder or other non- malignant organdisease or systemic disease or cancer secondary reaction, which may lead to highermedical risk and / or uncertainty of survival evaluation.

27. Known to be allergic to any PD-1 monoclonal antibody component.

28. Women of childbearing age who are unwilling or unable to use acceptable methods ofcontraception during the whole treatment period of this trial and within 12 weeksafter the last administration of the study drug (women of childbearing age include:any women who have had menarche, and have not undergone successful artificialsterilization (hysterectomy, bilateral tubal ligation, or bilateral ovariectomy),pregnancy or lactation Women; women with positive pregnancy test results at the timeof inclusion or before study drug administration; If the partner is a woman ofchildbearing age, the subject is a fertile male without effective contraceptivemeasures.