Recombinant Endostatin Combined With Vinorelbine and Cisplatin in Patients With Advanced Non-small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
The main object of this trial is to offer treatment of recombinant endostatin ( Sulijia) combined with Vinorelbine and Cisplatin (NP) plus maintenance therapy with Sulijia for advanced Non-small Cell Lung Cancer, expecting to improve progression free survival (PFS) , disease control rate(DCR) , objective response rate(ORR) and Overall survival (OS) compared with chemotherapy alone, and evaluate the efficacy and safety of Sulijia.

Detailed Description
-----------------
Recombinant endostatin injection Sulijia is a new type of recombinant protein drugs inhibiting tumor angiogenesis developed by a group of Chinese scientists and clinician. It is expressed in E. coli which Consists of 184 amino acids. It appears to be better than NP chemotherapy alone in terms of efficacy in phase I/II trials for advanced NSCLC. In this study, a randomized, double-blind, Placebo plus NP as control, multi-center phase III trial was designed to evaluate the safety and efficacy of Sulijia plus NP in the treatment of advanced NSCLC patients. PFS (progress free survival) is the primary end-point with OS (overall survival), ORR (objective response), DCR (disease control rate) and safety as the secondary end-point. A total of 560 patients have been recruited.

Official Title
-----------------
Recombinant Endostatin With Vinorelbine and Cisplatin (NP) Plus Maintenance Therapy With Recombinant Endostatin for Advanced Non-small Cell Lung Cancer: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Study

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

Intervention / Treatment
-----------------
* Drug: Placebos
* Drug: Sulijia


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female aged 18 to 70 years old; Patients with histological confirmed stage IV NSCLC; According to the standard of RECIST1.1, they should have at least one of accurately measurable lesions with the largest diameter >=10mm by spiral CT, PET-CT, with the largest diameter >=20mm by ordinary CT and MRI; general condition ECOG performance scale (PS) 0-1; Life expectancy of more than 3 months; No major organ dysfunction and laboratory indicators should meet the following requirements: absolute neutrophil count > 1.5*10^9/L, platelet count> 90*10^9/L, hemoglobin> 9g/dL; liver function: serum bilirubin was less than 2* maximum normal value; ALT and AST were less than 2.5*maximum normal value; BUN, Cr within 80% of normal range; Patients could understand the circumstances of this study and those who have signed the informed consent form. Exclusion Criteria: Receive the treatment of other experimental trials in the same period; on the medication of other anticancer drugs at the same time; Patients who have uncontrolled brain metastasis; Suffered from any other malignant tumors in the five years except for complete cure of cervical carcinoma in situ, basal cell cancer; Pregnant or lactating women; Severe infected patients; Patients who have serious cardiovascular disease such as coronary heart disease, unstable cardiac angina and high blood pressure; Patients who have vein thrombus; Patients who have psychiatric illness; Patients who are allergic to E. coli preparation; Researchers believe that those who do not fit.

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

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vinorelbine plus Cisplatin With placebos<br>The control group | Drug: Placebos<br>* Drug 1: Placebo(Sodium Chloride Injection),7.5mg/m2 on d1-d14 in each 21-day cycle（stop interventing until the disease progress） Drug 2: Vinorelbine-Cisplatin: Vinorelbine, 25mg/m2, iv, on d1 and d8 in each 21-day cycle (no more than 4 cycles); Cisplatin,75mg/m2, iv, on d1 in each 21-day cycle(no more than 4 cycles)<br>* Other names: Sodium Chloride Injection;|
| Experimental: Vinorelbine plus Cisplatin With Sulijia<br>The treatment group | Drug: Sulijia<br>* Drug 1: Sulijia(Recombinant Endostatin Injection) Sulijia, 7.5mg/m2 on d1-d14 in each 21-day cycle（stop interventing until the disease progress） Drug 2: Vinorelbine-Cisplatin: Vinorelbine, 25mg/m2, iv, on d1 and d8 in each 21-day cycle (no more than 4 cycles); Cisplatin,75mg/m2, iv, on d1 in each 21-day cycle(no more than 4 cycles)<br>* Other names: Recombinant endostatin injection;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival(PFS) | A duration from date of randomization until the date of first documented progression (as defined by RECIST 1.1) or date of death from any cause, whichever came first. A participant will be censored at the last date they are known not to be progressed. | Assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate(ORR) | Objective Response Rate is defined as the proportion of patients with complete response(CR) or partial response(PR) (as defined by RECIST 1.1). | Assessed up to 24 months | 
| Disease control rate(DCR) | Disease Control Rate is defined as the proportion of patients with complete response(CR), partial response(PR), or stable disease(SD) (as defined by RECIST 1.1). | Assessed up to 24 months | 
| Overall survival(OS) | Overall Survival is assessed via calculation of the time to death due to any cause. A participant will be censored at the last date they are known to be alive. | Assessed up to 72 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Non-small Cell Lung Cancer, Sulijia, Recombinant endostatin, Vinorelbine, Cisplatin