anlotinib versus docetaxel as the second-line treatment in egfr wild type patients with advanced nsclc

Conditions: Lung Cancer; Lung Cancer Metastatic

Summary: this study is conducted to explore the safety and efficacy of anlotinib, a tyrosine kinase inhibitors of vascular endothelial growth factor receptor 2（vegfr）、fgfr（fibroblast growth factor receptor）, platelet-derived growth factor receptor（pdgfr） and c-kit, vs docetaxel in advanced non-squamous non-small cell lung cancer harbouring wild-type epidermal growth factor receptor (egfr) .

this is a multicentre randomised controlled clinical trial conducted in china to compare the efficacy and and safety of anlotinib vs docetaxel in patients of egfr mutation-negative advanced nonsquamous non-small cell lung cancer. eligible patients will be randomized to arm a and arm b: arm a: patients on the anlotinib arm received 12mg anlotinib orally daily on day 1 to 14 of a 21-day cycle. arm b: patients on the docetaxel arm received 75mg/m2 docetaxel as intravenous infusion on day 1 of a 21-day cycle.

Eligibility criteria:
inclusion criteria: * -≥ 18 and ≤ 70 years of age. signed the informed consent form prior to patient entry * histologically or pathologically confirmed non-squamous non-small cell lung cancer(nsclc) with stage iv . * histologically or pathologically confirmed non-squamous non-small cell lung cancer(nsclc) with stage iv . * patients who has failed from the first-line platinum-based doublet chemotherapy harbouring epidermal growth factor receptor(egfr) sensitive mutations negetive, confirmed by pathological or blood test results) ）,alk/ros1 mutation-negative or unknown (for recurrent patients, adjuvant chemotherapy, neoadjuvant chemotherapy or neoadjuvant chemotherapy plus adjuvant were assessed for eligibility, and the last treatment time must be more than 6 months before enrollment） noted: failed from prior treatment means(1) progress disease confirmed by ct; cannot tolerable from standard treatment, such as hematologic toxicities ≥ level 4; non-hematologic toxicities ≥ level 3;damages of heart/liver/kidney ≥ level 2 in ctc ae 4.0 * must have at least one measurable lesion as per recist 1.1 defined as a lesion that is 10mm in longest diameter imaged by ct scan or mri；prior topical treatment, such as radiotherapy cryosurgery to the lesions is not allowed in less than 3 months; * life expectancy ≥3 months. * eastern cooperative oncology group(ecog) performance status 0 or 1. * toxicity caused by prior anti-cancer treatments was restored to ≤ level 1 in ctc ae (4.0) , except alopecia; * the blood routine examination need to be standard (no blood transfusion and blood products within 14 days, no g-csf and other hematopoietic stimulating factor correction); hemoglobin（hb）≥90 g/l; a neutrophil count of （anc）≥1.5×10e9/l; a platelet count of （plt）≥80×10e9/l; a total bilirubin (tbil) of ≤1.5 upper normal limitation (unl); a alanine aminotransferase (alt) and a aspartate aminotransferase (ast) of ≤2.5 unl, in case of liver metastasis alat and asat≤5 unl; a creatinine (cr) of ≤1.5 unl; a creatinine clearance rate ≥ 60ml/min (cockcroft-gault); * the woman patients of childbearing age who must agree to take contraceptive methods during the research and within another 8 weeks after it 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 8 weeks voluntarily joined the study and signed informed consent, with good compliance and follow-up. exclusion criteria: * -mixed lung cancer (including small cell cancer and other kinds of cancer mixed with non-small cell cancer, adenocarcinoma mixed with squamous cell carcinoma * no squamous nsclc with hemoptysis (\>50ml/day); * treated by taxel or similar drugs in 12months; * symptoms of brain metastases cannot be controlled and treated within less than 2 months * tumor locate within a distance of less than 5 mm from the large vessels, less than 2 cm from the bronchial tree, or has invaded local large vessels; tumor with cavum or necrotic obviously; * uncontrolled hypertension (systolic ≥140mmhg and/or diastolic ≥90mmhg, despite optimal drug therapy). * patients with with grade ⅱ myocardial ischemia or myocardial infarction, poor control of arrhythmias (including qtc interval male ≥ 450 ms, female ≥470 ms); according to nyha standard, grade ⅲ \~ ⅳ heart failure, or cardiac color doppler ultrasound examination showed left ventricular ejection fraction (lvef) \<50%. * coagulation dysfunction (inr\> 1.5, pt\> uln +4s or aptt\> 1.5 uln), with bleeding tendency or ongoing thrombolysis or anti-blood coagulation treatment;note: note: under the premise of international normalized ratio (inr) of prothrombin time (pt) less than or equal to 1.5, allow to administrate low-dose heparin (adult daily dose is 06000 \~ 12000 u) or low-dose aspirin (100 mg daily dosage or less) , for prophylactic purposes * patients whose routine urine tests indicate that urine protein ≥ ++ or verifies that the 24-h urine protein quantitation ≥ 1.0 g. * patients whose has peripheral neuropathy over level 2 in ctc ae4.0, except trauma. * patients with respiratory syndrome (difficulty breathing of level 2 or higher ), serous cavity effusion need to surgical treatment ( including pleural of level 2 or higher with respiratory distress and anoxia * patients who have unhealed wounds or fractures for a long time. * patients with severe infections , and need to receive systemic antibiotic treatment * decompensated diabetes or other contraindication with high dose glucocorticoid therapy; * cirrhosis or decompensated liver disease; active or untreated hepatitis c and/or hepatitis b virus (hbv) infection（prior hepatitis b history, hbsag positive and hbv dna≥500iu/ml; hcv rna positive and hepatic insufficiency * has an obvious factor influencing oral drug absorption, such as unable to swallow, chronic diarrhea and intestinal obstruction, etc * patients who received major surgical operations or experienced severe traumatic injuries, bone fracture, or ulcers within 4 weeks before screening. * severe weight loss (\> 10%) within 6 weeks before random * patients who had obvious hemoptysis (\>50ml/day) within 3 months before screening; patients who experienced bleeding symptoms of clinical significance within 3 months before screening, or with confirmed bleeding tendency such as hemorrhage of digestive tract, hemorrhagic gastric ulcer, baseline occult blood in stool ++ and above, or vasculitis, etc; * patients who manifested arterial/venous thrombus events, e.g. cerebrovascular accident (including transient ischemic attack), deep venous thrombosis and pulmonary embolism, etc., within 12 months before screening. * allergic reactions to anotol or excipients in experimental drugs. * allergic reactions to contrast medium * patients have participated in other antitumor drug clinical trials within 4 weeks before enrollment or prepare to receive systemic anti-tumor treatment during the study or within 4 weeks before randomization * patients with any other medical condition or reason, in that investigator's opinion, makes the patient unstable to participate in a clinical trial.