To Predict Efficacy by Detecting Circulating Endothelial Cell Subsets and Blood Perfusion Parameters Changes in Vivo Tumor in the Phase II/III Study of Anlotinib in Patients With Advanced Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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To reveal changes of peripheral markers and blood perfusion parameters in vivo tumor in the phase II study of anlotinib in patients with advanced non-small cell lung cancer. To clarify the meaning of peripheral markers and blood perfusion parameters in vivo tumor in predicting the effect of anti-angiogenic therapy.

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Anlotinib
* Drug: Placebo Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathology diagnosed with advanced NSCLC with measurable lesions; Have failed for 2 lines of chemotherapy; 3.18-70 years,ECOG PS:0-2,life expectancy of more than 3 months; 4.Other cytotoxic drugs,radiation therapy,or surgery≥4 weeks; 5.Main organs function is normal; 6.Women of childbearing age should take contraceptive measures during the study and within 6 months after end. Exclusion Criteria: SCLC(including mixed with NSCLC); The central cavity of Squamous cell carcinoma and hemoptysis with NSCLC; Patients failed to use the anti-tumor angiogenesis therapy; Patients have many influence factors toward oral medications ; Brain metastases patients accompanied by symptoms or symptom control for less than two months; Patients with severe and failed to controlled diseases,including: suboptimal blood pressure control;suffering from myocardial ischemia or above grade I myocardial infarction, arrhythmias and Class I heart failure;activity or failure to control severe infections;liver disease such as cirrhosis, decompensated liver disease, chronic active hepatitis;poorly controlled diabetes (FBG>10mmol/L);urine protein≥++,etc. Patients failed to heal wounds or fractures for Long-term; 4 weeks before enrollment, patients appeared NCI CTC AE grading >1 pulmonary hemorrhage; 4 weeks before enrollment, patients who appeared NCI CTC AE grade> 2 had other parts of the bleeding; patients have a tendency to bleed (e.g active peptic ulcer) or are receiving thrombolytic or anticoagulant therapy such as Warfarin, heparin or its analogues; Patients occurred venous thromboembolic events within 6 months; Patients who have HIV-positive or organ transplantation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anlotinib<br>Anlotinib QD orally and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent | Drug: Anlotinib<br>* Anlotinib QD<br>|
| Placebo Comparator: Placebo Capsule<br>Placebo capsule QD orally and it should be continued until disease progression or patients withdrawal of consent | Drug: Placebo Capsule<br>* Placebo capsule QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of circulating endothelial cell subsets（ total CECs 、 aCECs、apopCECs, etc.) | To detect number of circulating endothelial cell subsets（ total CECs 、aCECs、apopCECs, etc.) by Flow Cytometry; | Different time points before and after treatment of anlotinib,an expected average of 3 weeks | 
| The strength of intratumoral blood perfusion index (BV, BF, PS and MTT) . | To detect the strength of intratumoral blood perfusion index(BV, BF, PS and MTT) by CT perfusion imaging. | Different time points before and after treatment of anlotinib,an expected average of 3 weeks |