Apatinib Combined With Docetaxel Monotherapy as Second-line Therapy of Advanced EGFR WT, Non-squamous NSCLC

Inclusion Criteria:

* Aged ≥18 years old
* Pathologically Confirmed advanced (stage IIIB, and IV) non-squamous, non-small cell lung cancer, with measurable lesions (long diameter of tumor lesion according to CT scanning ≥10 mm, short diameter of lymph nodes according to CT scanning ≥15 mm, thickness according to CT scanning no more than 5 mm, measurable lesions which have not been treated with radiotherapy, cryotherapy or other local treatment)
* EGFR mutation detection confirmed EGFR mutation negative (EGFR wild-type)
* The patients have completed at least 2 cycles of first-line combined chemotherapy (including a platinum-based chemotherapy, 2-week or 3-week regimen). Efficacy evaluation indicates PD. No more than 28 days has passed since the last chemotherapy cycle. Patients who previously received treatment with EGFR-TKI could be included
* ECOG Score: 0-3
* Expected survival period ≥ 3 months
* The damages caused by other treatments have been recovered (NCI-CTCAE version 4.0 grading ≤ grade 1), the interval for administration of nitrourea or mitomycin ≥ 6 weeks, or administration of other cytotoxic drugs bevacizumab (Avastin), radiotherapy or surgery ≥ 4 weeks, or administration of EGFR TKI molecular target drugs ≥ 2 weeks
* Functions of major organs are normal, i.e. the following criteria should be met:

  1. Routine blood test results meet the criteria (no blood transfusion or use of blood products, and no use of G-CSF or other hematopoietic stimulating factors within 14 days)

     1. HB≥90 g/L
     2. ANC≥15×10\^9/L
     3. PLT≥80×10\^9/L
  2. The following criteria should be met in the biochemical tests:

     1. TBIL\<1.5×ULN
     2. ALT and AST\<2.5×ULN;for patients with liver metastasis, ALT and AST \>5×ULN
     3. Serum Cr≤1.25×ULN or Endogenous creatinine clearance rate\>45 ml/min (Cockcroft-Gault formula)
* Women of childbearing age should have taken reliable contraceptive measures, or received pregnancy test (serum or urine) with a negative result within 7 days before being included, and are willing to take appropriate contraceptive measures during the trial and within 8 weeks after last dose of the study drug. Males who have not received sterilization operation should agree to take appropriate contraceptive measures during the trial and within 8 weeks after last dose of the study drug
* The subjects are voluntary to join this study. They have signed the Informed Consent Form and are willing to coordinate with the follow-up with good compliance.

Exclusion Criteria:

* Patients with quamous carcinoma (including adenosquamous carcinoma ); small cell lung cancer (including small cell cancer and non-small cell mixed lung cancer)
* Patients with active brain metastasis, carcinomatous meningitis, or spinal compression, or disease of brain or pia mater according to the screening test, imaging, CT or MRI tests (patients who have completed the treatment and in a stable condition 21 days before screening could be included, but brain MRI, CT or venography is required to confirm that there are no brain hemorrhage symptoms)
* Imaging (CT or MRI) results indicate that the distance between the tumor and the large vessel ≤ 5 mm, or the existence of central tumors locally invading the large vessel could be detected
* Imaging (CT or MRI) indicates apparent pulmonary cavity or necrotizing tumors.
* Hypertension out of control (systolic pressure≥140 mmHg or diastolic pressure≥90 mmHg, despite optimal drug therapy)
* Patients with myocardial ischemia or myocardial infarction above grade II, or arrhythmia out of control (including QTc interval ≥450 ms for males and ≥470 ms for females)
* Patients with cardiac insufficiency grade III\~IV according to NYHA standard, or cardiac color ultrasound indicated LVEF \<50%
* Abnormal blood coagulation function (INR\>1.5 or prothrombin time (PT)\>ULN+4 seconds, or APTT \>1.5 ULN), with bleeding tendency or ongoing thrombolysis or anti-blood coagulation treatment
* Patients treated with anticoagulation agents or Vitamin K antagonist such as Warfarin, heparin, or other similar drugs
* Patients who had obvious hemoptysis within 2 months before screening, or experienced daily hemoptysis with a volume more than half a tea spoon (2.5ml) or above
* 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
* Known genetic or acquired bleeding or bleeding tendency (such as hemophilia, blood coagulation dysfunction, thrombocytopenia, and hypersplenism, etc.)
* Patients who have unhealed wounds or fractures for a long time
* Patients who received major surgical operations or experienced severe traumatic injuries, bone fracture, or ulcers within 4 weeks before screening
* Patients with obvious factors affecting absorption of oral drugs, such as difficulties in swallowing, chronic diarrhea and intestinal obstruction, etc
* Occurrence of abdominal fistula, gastrointestinal perforation, or intraperitoneal abscess within 6 months before screening
* Patients whose routine urine tests indicate that urine protein ≥ ++ or verifies that the 24-h urine protein quantitation ≥ 1.0 g
* Patients with clinical symptoms, or dropsy of serous cavity requiring surgical treatment (including hydrothorax, ascites, and hydropericardium)
* Patients who have a history of psychotropic drug abuse and are unable to break the habit, or who have a psychogeny
* Patients who have taken part in other drug clinical tests within 4 weeks before screening
* Confirmed ALK genetic abnormality (gene fusion or mutation)
* Patients who formerly suffered from or currently are complicated with other uncured malignant tumors, except basal cell carcinoma, carcinoma in situ of cervix and superficial bladder cancer that have been cured
* Patients who received the treatment with potent CYP3A4 inhibitors within 7 days before screening, or potent CYP3A4 inducers within 12 days before being included
* Pregnant or lactating women, fertile patients who are unwilling or unable to take effective contraceptive measures
* Conditions determined by investigators to possibly affect the clinical study or determination of the study results