Combine Apatinib Mesylate With PD-1 Antibody SHR-1210 for HCC With High Risk of Recurrence After Radical Resection

This is an interventional treatment trial for Hepatocellular Carcinoma Read More

Inclusion Criteria:

1. Age between 18-75 years old.
2. Patients were primary Hepatocellular carcinoma according to standardization of diagnosis and treatment for Hepatocellular carcinoma(2017 edition)
3. The imaging examination confirmed complete response (CR) after 1 month radical surgery ,and consented to postoperative adjuvant therapy
4. Preoperative imaging (CT/MRI/PET-CT), intraoperative or postoperative pathology confirmed HCC patients with high risk of disease recurrence contained microsatellite lesions, microvascular invation(MVI) or secondary and above portal vein branches tumor thrombosis (PVTT) after radical resection.
5. Preoperative imaging and perioperative outcomes confirmed no lymph node metastasis and distant metastasis.
6. Child-Pugh A.
7. No anti-tumor treatment before radical hepatic resection.
8. BCLC A-B
9. Eastern Cooperative Oncology Group(ECOG) body condition score 0-1.

10. Adequate main organ function:

    Hemoglobin ≥ 90g/L. Absolute neutrophil count (ANC) ≥ 1,500/mm3. Platelets ≥ 100,000/ul. Albumin ≥ 29g/L. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 3 the upper limit of normal (ULN). Total bilirubin (TBIL) ≤ 1.5 ULN. Creatinine ≤ 1.5 ULN.

11. Women of childbearing age (generally 15-49 years of age) are required to have a negative pregnancy test (serum or urine) within 14 days prior to enrollment, and will voluntarily use the appropriate method of contraception during the observation period and within 8 weeks after the last administration of the study drug; For men, appropriate methods of contraception should be used during the observation period and within 8 weeks after the last administration of the study drug.
12. Be willing and able to provide written informed consent for the study.

Exclusion Criteria:

1. History of liver transplantation.
2. Tumor rupture or invasion of adjacent organs.
3. History of immunosuppressive drugs used for 14 days prior to the first use of SHR-1210, excluding nasal and inhaled corticosteroids or physiological doses of systemic steroid hormones .
4. Subjects are allergic to Apatinib Mesylate Tablets, SHR-1210, pharmaceutical excipients, o other monoclonal antibodies.
5. Attenuated Live Vaccine in four weeks before study or during study.
6. Uncontrolled or symptomatic active central nervous system (CNS) metastases (if these patients have been treated to clinically stable and discontinuation of anticonvulsants and steroids in four weeks before study may be enrolled).
7. Peripheral neuropathy grade> 1.
8. History of autoimmune disease(Subjects with vitiligo or asthma in childhood but complete remission after adult intervention after adulthood may be enrolled)
9. Subjectes diagnosed any other malignant tumor within 3 years prior to study, except for adequately treated basal or squamous cell skin cancer or cervical carcinoma in situ
10. History of Human Immunodeficiency Virus (HIV).
11. Cardiovascular disease: Myocardial infarction, severe/unstable angina, NYHA class 2 or higher cardiac dysfunction, poorly controlled arrhythmias (including QTcF interval men >450 ms, women >470 ms, QTcF interval calculated by Fridericia formula), symptomatic hyperemia Sexual heart failure, cerebrovascular accident (including transient ischemic attack or symptomatic pulmonary embolism)
12. High blood pressure, and can not be well controlled by antihypertensive drugs (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90 mmHg)
13. Abnormal coagulation (INR > 1.5 × ULN or activated partial thromboplastin time (APTT) > 1.5 × ULN), with bleeding tendency or receiving thrombolysis or anticoagulant therapy.
14. Hereditary or acquired bleeding and thrombosis trends, such as: hemophilia, coagulopathy, thrombocytopenia, hypersplenism, etc.
15. Obvious hemoptysis in the first 2 months before the study or daily hemoptysis exceed 2.5ml.
16. Significant clinically bleeding symptoms or clear bleeding tendency within 3 months prior to the study, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood (++) and above, or vasculitis.
17. Artery/ venous thrombosis, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism,etc.
18. Long-term anticoagulant therapy with warfarin or heparin or antiplatelet therapy (aspirin ≥ 300 mg/day or clopidogrel ≥ 75 mg/day).
19. Severe infection within 4 weeks prior to first drug administration (eg, intravenous infusion of antibiotics, antifungal or antiviral drugs), or unexplained fever >38.5℃ during screening period/first drug administration.
20. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
21. Participated in any other drug clinical study within 4 weeks prior to first drug administration , or no more than 5 half-lives from the last study.
22. History of psychotropic substance abuse or drug abuse.
23. Sserious physical or mental illness, laboratory abnormalities, increasing risk of participating in the study, interfere with the results of the study, and patients considered by the investigator to be unfit for the study.