For local relapse not amenable to reasonable curative surgery or for those with metastatic chordoma, chemotherapy is recognised as inactive. The major study drug is the small molecular tyrosine kinase inhibitors targeted at the stem cell factor receptor (KIT) and the platelet-derived growth factor receptors (PDGFRA and PDGFRB), eg. imatinib. Anlotinib is a novel tyrosine kinase inhibitor targeting both at VEGFR-2, -3 and PDGFRA and PDGFRB with high affinity, which also showed broad antitumor activity against EGFR and so on. Thus this multicenter, two-armed phase II trial of PKUPH-sarcoma 05 intended to investigate the efficacy and safety of anlotinib versus imatinib on advanced chordoma.

Inclusion Criteria:

• 18 years and older;
• histologically proven metastatic or locally advanced chordoma, reviewed by the Pathology Committee of Peking University People's Hospital;
• not amenable to curative-intent surgery;
• measurable with computed tomography scan or magnetic resonance imaging, per RECIST, version 1.1.

Exclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG)30 performance status more than 2 ;
• life expectancy less than 12 weeks;
• with severe or uncontrolled medical disorders (≥grade 2 of Common Terminology Criteria for Adverse Events version 4.03 [CTCAE version 4.03]) that could jeopardise the outcomes of the study, for example, cardiac clinical symptom or disease with LVEF (left ventricular ejection fraction) <50%, hypertension that could not be well controlled through antihypertensive drugs and so on;
• weight loss of 20% or more before illness;
• brain or leptomeningeal metastasis;
• surgical procedure or radiotherapy within 4 weeks of enrollment;
• active gastroduodenal ulcer, previous condition associated with risk of bleeding or requiring anticoagulation;
• proteinuria or hematuria;
• denutrition with albuminemia less than 25 g/L;
• pregnant or breastfeeding status;
• other malignancy, positive HBV/HCV/HIV serology;
• known allergy to the experimental agents;
• had ever used anti-angiogenesis TKIs.