Eligible patients should have the following characteristics: age >16 years; diagnosis of high-grade osteosarcoma 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); Eastern Cooperative Oncology Group performance status 0-1 with a life expectancy >3 months; adequate renal, hepatic, and hemopoietic function. Additionally, the investigators require normal or controlled blood pressure, as well as surgery and/or radiotherapy completion at least 1 month before enrollment. All enrolled patients showed radiological evidence of disease progression and the lesion could be evaluated according to RECIST 1.1 before treatment start.