An Exploration of Apatinib Combined With S-1 in Patients With Advanced Non-small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
This study is to explore the potential efficacy and safety of low-dose Apatinib combined with S-1 in patients with advanced lung cancer. Patients with advanced NSCLC will be treated with oral apatinib and S-1 after treatment failure of standard regimen.

Detailed Description
-----------------
Apatinib is a tyrosine kinase inhibitor which selectively inhibits the vascular endothelial growth factor receptor-2 (VEGFR-2). The anti-angiogenesis effect of apatinib has been proved in preclinical tests. Phase II study has showed an improvement of progression free survival in pretreated patients. S-1, an oral fluoropyrimidine has considerable effectiveness with mild side effect in patients failed to standard treatments. The purpose of this study is to evaluate the potential efficacy and safety of low-dose Apatinib combined with S-1 in heavily pretreated patients with advanced lung cancer. And to explore the biomarkers of antiangiogenesis therapy and the possible mechanisms of treatment resistance on the basis of next generation sequencing.

Official Title
-----------------
An Exploratory Study of Low-dose Apatinib Combined With S-1 in Patients With Advanced Non-small Cell Lung Cancer

Conditions
-----------------
Non-small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: Apatinib Mesylate tablet combined with S-1 capsules


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pathologically confirmed Non-small cell lung cancer Patients with extracranial measurable lesions Patients with NSCLC failed for standard treatments Eastern Cooperative Oncology Group performance status score: 0 2 and life expectancy of more than 3 months Major organs functioning properly Compliance is good and agreed to cooperate with the survival of follow-up Informed consent Exclusion Criteria: Contraindications for investigational agents Patients with clinical symptoms of brain metastases or meningeal metastasis Tumor invade big vessels or close to big vessels Uncontrolled hypertension Abnormal coagulation (INR>1.5 or Prothrombin Time>ULN+4, or Activated Partial Thromboplastin Time>1.5 ULN), bleeding tendency or receiving coagulation therapy Hemoptysis, more than 2.5ml daily Thrombosis in 12 months, including pulmonary thrombosis, stoke, or deep venous thrombosis. Myocardial ischemia or infarction more than stage II, cardiac insufficiency. Received big surgery, had bone fracture or ulcer in 4 weeks. Urine protein≥++, or urine protein in 24 hours≥1.0g

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apatinib & S-1<br>Apatinib Mesylate tablet combined with S-1 Capsules Apatinib Mesylate tablet 250mg once daily combined with S-1(Tegafur,Gimeracil and Oteracil Potassium Capsules) 40mg 60mg twice daily by mouth, d1-14, repeated every 3 weeks. | Drug: Apatinib Mesylate tablet combined with S-1 capsules<br>* Oral use with low-dose Apatinib combined with S-1 until disease progression<br>* Other names: Apatinib combined with S-1;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival(PFS) | PFS is defined as the length of time from random assignment to disease progression or to death resulting from any cause other than the progress. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival(OS) | Overall Survival is defined as the length of time from random assignment to death or to last contact. | 2 years | 
| Objective response rate(ORR) | Objective response rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response according to Response Evaluation Criteria in Solid Tumors 1.1（RECIST1.1） | 2 years | 
| Disease Control Rate(DCR) | Disease Control Rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response + Stable Disease according to radiological assessments. | 2 years | 
| Adverse Events(AEs) | AEs are evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events v4.0. | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
S1, non-small cell lung cancer, Apatinib