An Exploration of Apatinib Combined With S-1 in Patients With Advanced Non-small Cell Lung Cancer

An Exploratory Study of Low-dose Apatinib Combined With S-1 in Patients With Advanced Non-small Cell Lung Cancer

This study is to explore the potential efficacy and safety of low-dose Apatinib combined with S-1 in patients with advanced lung cancer. Patients with advanced NSCLC will be treated with oral apatinib and S-1 after treatment failure of standard regimen.

Apatinib is a tyrosine kinase inhibitor which selectively inhibits the vascular endothelial growth factor receptor-2 (VEGFR-2). The anti-angiogenesis effect of apatinib has been proved in preclinical tests. Phase II study has showed an improvement of progression free survival in pretreated patients. S-1, an oral fluoropyrimidine has considerable effectiveness with mild side effect in patients failed to standard treatments. The purpose of this study is to evaluate the potential efficacy and safety of low-dose Apatinib combined with S-1 in heavily pretreated patients with advanced lung cancer. And to explore the biomarkers of antiangiogenesis therapy and the possible mechanisms of treatment resistance on the basis of next generation sequencing.

Inclusion Criteria:

• Pathologically confirmed Non-small cell lung cancer
• Patients with extracranial measurable lesions
• Patients with NSCLC failed for standard treatments
• Eastern Cooperative Oncology Group performance status score: 0~2 and life expectancy of more than 3 months
• Major organs functioning properly
• Compliance is good and agreed to cooperate with the survival of follow-up
• Informed consent

Exclusion Criteria:

• Contraindications for investigational agents
• Patients with clinical symptoms of brain metastases or meningeal metastasis
• Tumor invade big vessels or close to big vessels
• Uncontrolled hypertension
• Abnormal coagulation (INR>1.5 or Prothrombin Time>ULN+4, or Activated Partial Thromboplastin Time>1.5 ULN), bleeding tendency or receiving coagulation therapy
• Hemoptysis, more than 2.5ml daily
• Thrombosis in 12 months, including pulmonary thrombosis, stoke, or deep venous thrombosis.
• Myocardial ischemia or infarction more than stage II, cardiac insufficiency.
• Received big surgery, had bone fracture or ulcer in 4 weeks.
• Urine protein≥++, or urine protein in 24 hours≥1.0g