Apatinib Plus Anti-PD1 Therapy for Advanced Osteosarcoma

Inclusion Criteria: * age more than or equal to 11 years; * diagnosis confirmed histologically and reviewed centrally; * prior treatment (completed \>4 weeks before trial entry) consisted of standard high-grade osteosarcoma chemotherapy agents including doxorubicin, cisplatin, high- dose methotrexate, and ifosfamide; metastatic relapsed and unresectable progressive disease (PD); * having measurable lesion according to RECIST 1.1; * Eastern Cooperative Oncology Group performance status 0-1 with a life expectancy \>3 months; * Patients must have adequate organ function (without blood transfusion, without growth factor or blood components support within 14 days before enrollment)as determined by: Hemoglobin ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet count ≥ 75×109/L (for patients with advanced hepatocellular carcinoma), Platelet count ≥ 100×109/L (for patients with advanced gastric cancer); serum albumin ≥2.8 g/dL; serum total bilirubin (TBIL)≤1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal(ULN), for subjects with liver metastases, ALT and AST≤5×ULN; Calculated creatinine clearance (CrCl) \> 50 mL/min (Cockcroft-Gault formula will be used to calculate CrCl). * normal or controlled blood pressure; * Females of childbearing potential (FOCBP), who are not surgically sterile or postmenopausal, must conduct pregnancy test (serum or urine) within 7 days before enrollment, and…