Chemotherapy Combined Autologous Cytokine-induced Killer Cells in Naive Stage IV EGFR-wild Type Lung Adenocarcinoma

Study Overview
=================
Brief Summary
-----------------
This is a prospective, randomized, open, multicenter phase Ⅱ study to evaluate the efficacy of cytokine-induced killer cells combined chemotherapy in stage Ⅳ naive EGFR wild-type lung adenocarcinoma.

Detailed Description
-----------------
There is still no great improvement in advanced EGFR wild-type lung adenocarcinoma although great progress was made in treatment of non-small cell lung cancer. It's necessary to explore the treatment mode of this kind of patients. As the progress was made in tumor immunity and immunotherapy, more and more cancer therapists accept the treatment model of chemotherapy combined immunotherapy. And now chemotherapy combined autologous CIK cells is one kind of common treatment model in some countries. Investigators try to evaluate the efficacy and safety of this kind of treatment model in patients with stage Ⅳ naive EGFR wild-type lung adenocarcinoma.

Official Title
-----------------
Chemotherapy Combined Autologous Cytokine-induced Killer Cells in Naive Stage IV EGFR-wild Type Lung Adenocarcinoma: A Prospective, Randomised, Open, Multicenter Phase Ⅱ Study

Conditions
-----------------
Lung Adenocarcinoma

Intervention / Treatment
-----------------
* Biological: CIK
* Drug: chemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosed as stage Ⅳ naive EGFR wild-type lung adenocarcinoma by image, tissue and/or cytology; or relapse after operation (if the patient received adjuvant chemotherapy and the interval between the last chemotherapy and relapse is at least six months. The detection method of EGFR mutation is ARMS. EML4-ALK fuse gene is negative and the detection of EML4-ALK is FISH or ventana IHC. There should be at least one measurable lesions (by CT or MRI) No other cancer history ( except skin squamous cell carcinoma after surgery) Age between 18 and 75 years old World health organization- Eastern Cooperative Oncology Group Performance Status 0-1 Life expectancy more than 3 months and can be followed-up Patients must have adequate organ and marrow functions as defined below: white blood cells: more than 3.5×109/L, Neutrophils: more than 1.5×109/L, Platelets: more than 80×109/L, Hemoglobin more than 90g/L, Serum total bilirubin less than 1.5 folds of the upper normal limit (ULN), Serum glutamic-oxal (o) acetic transaminase: less than 2.5×ULN (if there is liver metastasis less than 5×ULN); Serum creatinine: less than 1.0×ULN, Prothrombin time, Active partial thromboplastin time, Fibrinogen, Thrombin time are in normal ranges. Women of child-bearing period must take effective contraceptive measures during all the time of study. During the period of study the results of blood and urine pregnancy test should be negative. Men should take effective contraceptive measures from the beginning of therapy to one month after the last cycle of chemotherapy. Willing to comply with the ban and constraints for this study protocol specified. Informed consent and willing to participate in this study. Exclusion Criteria: Accepted other study drugs 30 days before the beginning of this study. Brain metastases with clinical symptoms ( with exception of being controlled after radiation) Active viral or bacterial infection and can't be controlled with appropriate anti-infection treatment Known as HIV infection, syphilis serology reaction positive, active hepatitis B virus or hepatitis C virus infection Suffering from mental illness or other illness, such as heart or lung disease, diabetes, etc. that can not be controlled, and can not be coped with study treatment and monitoring requirements. Known allergy to any kind of component of study drugs Active rheumatic diseases Organ transplant recipients Poor compliance Pregnant women Lactating women

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CIK combined chemotherapy group<br>autologous CIK combined chemotherapy group Drugs: platinum combined doublets; After 3 or 4 days of chemotherapy, about 5×109 autologous cytokine-indued killer cells are transfused into the vein of patients in one hour. | Biological: CIK<br>* platinum combined doublets: Paclitaxel 175mg/m2 D1, or Docetaxel75mg/m2 D1, or Pemetrexed Disodium 500mg/m2，D1；combined cisplatin 25mg/m2，D1-3 or carboplatin AUC=5, D1. After 3 or 4 days of chemotherapy, about 5×109 autologous cytokine-induced killer cells are transfused into the vein of patients in one hour.<br>* Other names: autologous cytokine-induced killer cells;Drug: chemotherapy<br>* platinum combined doublets: Paclitaxel 175mg/m2 D1, or Docetaxel75mg/m2 D1, or Pemetrexed Disodium 500mg/m2，D1；combined cisplatin 25mg/m2，D1-3 or carboplatin AUC=5, D1.<br>* Other names: platinum combined doublets;|
| Active Comparator: chemotherapy group<br>platinum combined doublets Drugs: Paclitaxel 175mg/m2 D1, or Docetaxel75mg/m2 D1, or Pemetrexed Disodium 500mg/m2，D1；combined cisplatin 25mg/ m2，D1-3 or carboplatin AUC=5, D1. | Drug: chemotherapy<br>* platinum combined doublets: Paclitaxel 175mg/m2 D1, or Docetaxel75mg/m2 D1, or Pemetrexed Disodium 500mg/m2，D1；combined cisplatin 25mg/m2，D1-3 or carboplatin AUC=5, D1.<br>* Other names: platinum combined doublets;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival time | overall survival time aims at from date of randomization until the date of death from any cause, up to 36 months | from the day of randomization to the day of death, up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to progression | time to progression points to from date of randomization until the date of first documented progression, up to 24 months | from the day of randomization to the day of first detecting progression, up to 24 months | 
| objective response rate | the partion of overall remission in total proportion | one year |