This phase II study was designed to assess the efficacy and safety of the combination of Apatinib, Tucidinostat (chidamide), a histone deacetylase inhibitor in relapsed or refractory osteosarcoma patients.

Inclusion Criteria:

1. Age ≥10 years, ≤ 75 years;
2. Histologically confirmed Advanced classic osteosarcoma with unresectable recurrence or metastatic disease ；
3. Prior treatment consisted of standard chemotherapy agents including doxorubicin, cisplatin, methotrexate, and ifosfamide;
4. Eastern Collaborative Oncology Group (ECOG) 0~2；
5. Tumor size is measurable according to RECIST1.1 criteria；
6. Adequate organ function；
7. Life expectancy is more than 3 months；
8. Willing and able to provide written informed consent.

Exclusion Criteria:

1. Previously exposed to histone deacetylase inhibitors or angiogenesis inhibitors;
2. Urine protein≥ ++;
3. FBG>10mmol/L;
4. Uncontrolled blodd pressure (ystolic blood pressure > 150 mmHg and/or diastolic blood pressure > 90 mmHg);
5. Known active CNS metastases and/or carcinomatous meningitis;
6. Not able to take medicine orally;
7. Coagulant function abnormality (PT>16s, APTT> 43s, TT>21s, FIB）<2g/L);
8. Uncontrolled clinically significant systemic diseases, including active infection, unstable angina, angina occurred within 3 months,≥ NYHA II congestive heart failure, myocardial infarction occurred within 6 months, severe arrhythmia, liver, kidney, or metabolic disease;
9. Major surgery received or severe traumatic injury, fracture, or ulcer occurred within 4 weeks of the first dose of study medication.