Study of Anlotinib in Patients With Advanced Non-small Cell Lung Cancer（ALTER0303）

Anlotinib (AL3818) is a kind of innovative medicines approved by State Food and Drug Administration（SFDA:2011L00661） which was researched by Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd. Anlotinib is a kinase inhibitor of receptor tyrosine with multi-targets, especially for VEGFR1、VEGFR2、VEGFR3、FGFR1/2/3、PDGFRa/β c-Kit and MET.

Inclusion criteria

• Signed and dated informed consent
• Diagnosed with advanced NSCLC (phase IIIB/IV) through pathology, with measurable nidus(using RECIST 1.1)
• at least two systematic chemotherapy with upwards of 3-line treatments or cannot suffer
• Patients must provide detectable specimen (from tumor tissue or hydrothorax) before participating, who negative in EGFR&ALK can participate or who positive in EGFR&ALK, have or have not drug tolerance after the treatment with relative targeted drugs
• ECOG PS：0-1,Expected Survival Time: Over 3 months
• main organs function is normal
• The woman patients of childbearing age who must agree to take contraceptive methods (e.g. intrauterine device, contraceptive pill or condom) during the research and within another 6 months after it; who are not in the lactation period and examined as negative in blood serum test or urine pregnancy test within 7 days before the research; The man patients who must agree to take contraceptive methods during the research and within another 6 months after it

Exclusion criteria

• have used Anlotinib before
• Small Cell Lung Cancer (including small cell cancer and other kinds of cancer mixed with non-small cell cancer)
• examined as positive in EGFR&ALK mutation detection and never take the treatment of TKIs
• central lung squamous carcinoma along with cavum, or non-small cell lung cancer along with hemoptysis (>50ml/day)
• other kinds of malignancies within 5 years or for now
• plan to take systemic anti-tumor therapy within 4 weeks before grouping or during the medicine-taking period of this research, including Cytotoxic Therapy, Signal Transduction Inhibitor, and Immunotherapy (or who use Mitomycin C within 6 weeks before taking the treatment with experimental drug); The patients who have already taken Extended Field Radiotherapy (EF-RT) within 4 weeks before grouping or Limited Field Radiotherapy with proposed assessment of nidus within 2 weeks before grouping
• have got non remissive toxic reactions derived from previous therapies, which is over level 1 in CTC AE (4.0), alopecia NOT included
• with kinds of factors which affect oral medicine (e.g. failing to swallow, gastrointestinal tract getting resected, chronic diarrhea and ileus)
• pleural effusion or ascites, resulting in respiratory syndrome (≥CTC AE level 2)
• symptoms of brain metastases cannot be controlled and treated within less than 2 months
• get any severe diseases or the ones that cannot be controlled
• take major surgical treatments, open biopsy, or get overt traumatic injury within 28 days before grouping
• have any habitus or medical history of hemorrhage, however severe it is; the patients who have non healing wounds, ulcer or fracture after any events with hemorrhage or bleeding (≥CTCAE level 3)
• get arterial/venous thrombosis within 6 months, such as cerebrovascular accidents (including temporary ischemic stoke), deevenous thrombosis, and pulmonary embolism
• ever abuse psychiatric drugs and cannot abstain or who are diagnosed with mental disorder
• have participated in other clinical trials of anti-tumor medicine within 4 weeks
• diagnosed with disease which will severely endanger the security of patients or influence the completion of this research.