Anlotinib Combined With Docetaxel Versus Docetaxel for Previous Treated Advanced NSCLC

Inclusion Criteria:

• 1. Subjects voluntarily joined the study and signed informed consent, with goodcompliance and follow-up;
• 2. Diagnosed as locally advanced and / or metastatic non-small cell lungadenocarcinoma (NSCLC) by cytology or histology; diagnosed as stage IIIB, IIIC or IVaccording to the 2017 new version of the UICC lung cancer staging criteria (8thedition);
• 3. At least one target lesion that has not received local treatment in the past 3months, and accurate measurement by magnetic resonance imaging (MRI) or computedtomography (CT) in at least 1 direction
• 4. first line chemotherapy used platinum-based doublet chemotherapy and failed.
• 5. Provide detectable specimens (tissue or cancerous pleural effusion) for genotypingbefore enrollment, and the patients should be with negative EGFR, ALK, and ROS1 genetest results;
• 6. 18~75 years old, ECOG PS 0-1 points. Life expectancy is at least 3 months.
• 7. The damage subjects received from other treatments has recovered(NCI-CTCAE version 4.0 grade ≤ 1), the interval of subjects receiving nitrosourea or mitomycin should beat least 6 weeks; the interval subjects receiving other cytotoxic drugs, bevacateAvastin (Avastin), surgery should be at least 4 weeks; the interval subjects receivingradiotherapy (except for local palliative radiotherapy) should be at least 2 weeks;
• 8. The main organs function are normally, the following criteria are met:

1. Blood routine examination criteria should be met (no blood transfusion and bloodproducts within 14 days, no correction by G-CSF and other hematopoietic stimuli):HB≥90 g/L; ANC ≥ 1.5×10^9/L; PLT ≥80×10^9/L;

2. Biochemical examinations must meet the following criteria: TBIL<1.5×ULN; ALT andAST < 2.5×ULN, and for patients with liver metastases < 5×ULN; Serum Cr ≤ 1.25×ULN or endogenous creatinine clearance > 60 ml/min (Cockcroft-Gaultformula).

• 9. Avoid pregnancy during treatment and 6 month after treatment.

Exclusion Criteria:

• 1. Small cell lung cancer (including lung cancer mixed with small cell lung cancer andnon-small cell lung cancer);
• 2. Have used anlotinib / docetaxel before, or have used other VEGFR-TKI drugs.
• 3. Imaging (CT or MRI) shows that the distance between tumor lesion and the largeblood vessel is ≤ 5 mm, or there is a central tumor that invades the local large bloodvessel; or there is a significant pulmonary cavity or necrotizing tumor;
• 4. History and comorbidities

1. Active brain metastases, cancerous meningitis, spinal cord compression, orimaging CT or MRI screening for brain or pia mater disease (a patient with brainmetastases who have completed treatment and stable symptoms in 28 days beforeenrollment may be enrolled, but should be confirmed by brain MRI, CT orvenography evaluation as no cerebral hemorrhage symptoms);

2. The patient is participating in other clinical studies or completing the previousclinical study in less than 4 weeks;

3. Other active malignancies that require simultaneous treatment;

4. Patients with a history of malignant tumors except for patients with cutaneousbasal cell carcinoma, superficial bladder cancer, cutaneous squamous cellcarcinoma or orthotopic cervical cancer who have undergone a curative treatmentand have no disease recurrence within 5 years from the start of treatment

5. Patients with previous anti-tumor treatment-related adverse reactions (excludinghair loss) who have not recovered to NCI-CTCAE ≤1;

6. Abnormal blood coagulation (INR > 1.5 or prothrombin time (PT) > ULN + 4 secondsor APTT > 1.5 ULN), with bleeding tendency or undergoing thrombolytic oranticoagulant therapy;

7. Note: Under the premise of prothrombin time international normalized ratio (INR) ≤ 1.5, low-dose heparin (adult daily dose of 0.6 million to 12,000 U) or low-doseaspirin (daily dosage ≤ 100 mg) is allowed for preventive purposes;

8. Renal insufficiency: urine routine indicates urinary protein ≥ ++, or confirmed 24-hour urine protein ≥ 1.0g;

9. Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic bloodpressure ≥90 mmHg, despite optimal medical treatment);

10. The effects of surgery or trauma have been eliminated for less than 14 daysbefore enrollment in subjects who have undergone major surgery or have severetrauma;

11. Severe acute or chronic infections requiring systemic treatment;

12. Suffering from severe cardiovascular disease: myocardial ischemia or myocardialinfarction above grade II, poorly controlled arrhythmias (including men with QTcinterval ≥ 450 ms, women ≥ 470 ms); according to NYHA criteria, grades III to IVInsufficient function, or cardiac color Doppler ultrasound examination indicatesleft ventricular ejection fraction (LVEF) <50%;

13. There is currently a peripheral neuropathy of ≥CTCAE 2 degrees, except fortrauma;

14. Respiratory syndrome (≥CTC AE grade 2 dyspnea), serous effusion (includingpleural effusion, ascites, pericardial effusion) requiring surgical treatment;

15. Long-term unhealed wounds or fractures;

16. Severe weight loss (greater than 10%) within 6 weeks prior to randomization;

17. Decompensated diabetes or other ailments treated with high doses ofglucocorticoids;

18. Factors that have a significant impact on oral drug absorption, such as inabilityto swallow, chronic diarrhea, and intestinal obstruction;

19. Clinically significant hemoptysis (daily hemoptysis greater than 50ml) within 3months prior to enrollment; or significant clinically significant bleedingsymptoms or defined bleeding tendency, such as gastrointestinal bleeding,hemorrhagic gastric ulcer, baseline fecal occult blood ++ and above, or sufferingfrom vasculitis;

20. Events of venous/venous thrombosis occurring within the first 12 months prior toenrollment, such as cerebrovascular accidents (including transient ischemicattacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, andpulmonary embolism;

21. Planned for systemic anti-tumor therapy, including cytotoxic therapy, signaltransduction inhibitors, immunotherapy (4 weeks prior to enrollment in otheranti-cancer drug clinical trials or within 4 weeks prior to grouping or duringthe study period Or use mitomycin C) within 6 weeks prior to receiving the testdrug. Radiation-rehabilitation radiotherapy (EF-RT) was performed within 4 weeksbefore grouping or limited-field radiotherapy to be evaluated for tumor lesionswithin 2 weeks before grouping.