SHR-1210 Combined With Apatinib Mesylate in the Perioperative Treatment of Hepatocellular Carcinoma
SHR-1210 Combined With Apatinib Mesylate in the Perioperative Treatment of Hepatocellular Carcinoma
This is a Phase II , Open-label , Investigator-initiated Trail of SHR-1210 (an Anti-PD-1
 Inhibitor) in Combination With Apatinib in Patients With Hepatocellular Carcinoma(HCC).This
 study aims to evaluate the safety and efficacy of SHR-1210 combination with Apatinib as a
 preoperative treatment of HCC.
This is an Open, Single Arm, Exploratory and Phase II Clinical Trial of Apatinib Combined
 With SHR-1210 (an Anti-PD-1 Inhibitor) in Patients With Hepatocellular Carcinoma(HCC) as
 Perioperative Treatment. we conduct this study in order to observe and evaluate the efficacy
 and safety of Apatinib combined with SHR-1210 (an Anti-PD-1 Inhibitor) in treatment of
 patients with HCC. Primary Efficacy Endpoint: Major pathologic response (MPR), Secondary
 Efficacy Endpoints: Pathological complete response Rate (pCR), Objective Response(ORR)
 (According to RECIST Version 1.1), Recurrence-free survival(RFS) and Overall survival rate of
 6 months (OS %-6 m). Safety and tolerance will be evaluated by incidence, severity and
 outcomes of AEs and categorized by severity in accordance with the NCI CTC AE Version 4.0.3.
Inclusion Criteria:

 1. The patient volunteered to participate in the study and signed an informed consent
 form

 2. ≥18 years of age，Male or female

 3. Subjects are diagnosed with histologically or cytologically confirmed HCC

 4. Subjects haven't received any systemic treatment for HCC before admission.

 5. Subjects enrolled must have measurable lesion(s) according to the RECIST 1.1 standard

 6. ECOG performance status of 0 or 1

 7. Life expectancy ≥ 12 weeks

 8. Subjects are diagnosed with resectable stage IIB, stage IIIA HCC cancer.

 9. The main organ's function is normal and it should meet the following criteria(Excludes
 use of any blood components and cell growth factors during the screening period)

 1. Absolute neutrophil count≥1.5×109 /L

 2. Platelets≥80×109/L ;Hemoglobin≥9.0 g/dL; Serum albumin≥3g/dL

 3. Thyroid stimulating hormone (TSH)≤1.0×upper limit of normal(ULN)（If abnormal, T3
 and T4 levels should be examined at the same time）

 4. Total bilirubin (TBIL)≤1.5×upper limit of normal (ULN); ALT and AST≤1.5×upper
 limit of normal(ULN); AKP≤ 2.5×upper limit of normal(ULN)

 5. Serum creatinine ≤1.5×ULN or creatinine clearance > 60 mL/minute (using
 Cockcroft-Gault formula)

 Exclusion Criteria:

 1. Known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and lamellar
 cell carcinoma; other active malignant tumor except HCC within 5 years or
 simultaneously

 2. Be ready for or previously received organ or allogenic bone marrow transplantation

 3. Moderate-to-severe ascites with clinical symptoms

 4. History of gastrointestinal hemorrhage within 6 months prior to the start of study
 treatment or clear tendency of gastrointestinal hemorrhage.

 5. Abdominal fistula, gastrointestinal perforation or intraperitoneal abscess within 6
 months prior to the start of study treatment.

 6. Known genetic or acquired hemorrhage or thrombotic tendency.

 7. The patient is currently using or has recently used (within 10 days before the start
 of study treatment) aspirin (> 325mg / day (maximum antiplatelet dose) or
 dipyridamole, ticlopidine, clopidogrel and cilostazol.

 8. Thrombosis or thromboembolic event within 6 months prior to the start of study
 treatment.

 9. Cardiac clinical symptom or disease that is not well controlled.

 10. Subjects have uncontrollable hypertension (systolic pressure ≥ 140 mmHg or diastolic
 pressure ≥ 90 mmHg), despite patients have taken the best drug treatment ；Subjects
 have had a hypertensive crisis or hypertensive encephalopathy

 11. Patient develops severe vascular disease within 6 months before the start of study
 treatment.

 12. Patients with severe, unhealed or split wounds and active ulcers or untreated
 fractures

 13. Patients who underwent surgical treatment within 4 weeks prior to the start of study
 treatment.

 14. Factors to affect oral administration (such as patients unable to swallow oral
 medications, malabsorption syndrome etc. situations evidently affect drug absorption).

 15. Patients with gastrointestinal diseases such as intestinal obstruction (including
 incomplete intestinal obstruction) or those who may have caused gastrointestinal
 bleeding, perforation or obstruction.

 16. There is evidence of intragastric gas that cannot be explained by puncture or recent
 surgery.

 17. Previous or current presence of metastasis to central nervous system.

 18. Subjects have history of hepatic encephalopathy.

 19. The subject has an interstitial lung disease that is symptomatic or may interfere with
 the discovery or management of suspected drug-related lung toxicity; previous and
 current subjects with a history of pulmonary fibrosis, interstitial pneumonia,
 pneumoconiosis, drug-associated pneumonia, severe impaired lung function, etc.

 20. The patient has any active autoimmune disease or a history of autoimmune disease
 expected relapse.

 21. Severe infection within 4 weeks prior to the start of study treatment.

 22. A history of immunodeficiency, including HIV-positive or other acquired, congenital
 immunodeficiency disease.

 23. Prior therapy with any anti-PD-1/PD-L1 drug (specifically targeting T-cell
 co-stimulation or checkpoint pathways), Sorafenib or Apatinib.

 24. Subjects were vaccinated with live attenuated vaccine within 28 days before the first
 dose or expected to receive this vaccine within 60 days after the last dose or during
 the study period.

 25. Treatment of other investigational product(s) within 28 days prior to the start of
 study treatment.