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

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

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.

Study Overview

• Status: Terminated
• Conditions: Lung Adenocarcinoma
• Intervention / Treatment: Biological: CIK; Drug: chemotherapy

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.

• Study Type: Interventional
• Enrollment (Actual): 280
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Henan
    • ZhengZhou, Henan, China, 450008
      • Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. EML4-ALK fuse gene is negative and the detection of EML4-ALK is FISH or ventana IHC.
3. There should be at least one measurable lesions (by CT or MRI)
4. No other cancer history ( except skin squamous cell carcinoma after surgery)
5. Age between 18 and 75 years old
6. World health organization- Eastern Cooperative Oncology Group Performance Status 0-1
7. Life expectancy more than 3 months and can be followed-up

8. 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.

9. 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.
10. Men should take effective contraceptive measures from the beginning of therapy to one month after the last cycle of chemotherapy.
11. Willing to comply with the ban and constraints for this study protocol specified.
12. Informed consent and willing to participate in this study.

Exclusion Criteria:

1. Accepted other study drugs 30 days before the beginning of this study.
2. Brain metastases with clinical symptoms ( with exception of being controlled after radiation)
3. Active viral or bacterial infection and can't be controlled with appropriate anti-infection treatment
4. Known as HIV infection, syphilis serology reaction positive, active hepatitis B virus or hepatitis C virus infection
5. 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.
6. Known allergy to any kind of component of study drugs
7. Active rheumatic diseases
8. Organ transplant recipients
9. Poor compliance
10. Pregnant women
11. Lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CIK combined chemotherapy group; 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; 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.; Other Names: autologous cytokine-induced killer cells; Drug: chemotherapy; 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.; Other Names: platinum combined doublets
ACTIVE_COMPARATOR: chemotherapy group; 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; 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.; 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

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Collaborators: Henan Provincial People's Hospital; Hebei Medical University Fourth Hospital; Tangshan People's Hospital; Shanxi Dayi Hospital; Puyang Oilfield General Hospital; Nanyang Central Hospital; Shenma Medical Group General Hospital; First People's Hospital of Shangqiu; Xinyang Central Hospital; 150th Hospital of PLA; Anyang Regional Hospital; First Affiliated Hospital of Nanyang Medical College; Jiaozuo Tumor Hospital; The 152th Central Hospital of PLA
• Investigators: Study Director: Quanli Gao, M.D., Henan Cancer Hospital

Publications and helpful links

General Publications

• Li R, Wang C, Liu L, Du C, Cao S, Yu J, Wang SE, Hao X, Ren X, Li H. Autologous cytokine-induced killer cell immunotherapy in lung cancer: a phase II clinical study. Cancer Immunol Immunother. 2012 Nov;61(11):2125-33. doi: 10.1007/s00262-012-1260-2. Epub 2012 May 13.
• Zhong R, Teng J, Han B, Zhong H. Dendritic cells combining with cytokine-induced killer cells synergize chemotherapy in patients with late-stage non-small cell lung cancer. Cancer Immunol Immunother. 2011 Oct;60(10):1497-502. doi: 10.1007/s00262-011-1060-0. Epub 2011 Jun 17.
• Wang S, Wang Z. Efficacy and safety of dendritic cells co-cultured with cytokine-induced killer cells immunotherapy for non-small-cell lung cancer. Int Immunopharmacol. 2015 Sep;28(1):22-8. doi: 10.1016/j.intimp.2015.05.021. Epub 2015 May 23.
• Zhao L, Li W, Wang Z, Yang Y, Zhang Y, Shang Y, Ren X, Gao Q. Survival benefit from RectroNectin-activated cytokine-induced killer cells combined with chemotherapy in advanced EGFR wild-type lung adenocarcinoma. Immunotherapy. 2018 Mar 1;10(6):501-510. doi: 10.2217/imt-2017-0140.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2015
• Primary Completion (ACTUAL): September 1, 2018
• Study Completion (ACTUAL): September 1, 2018

Study Registration Dates

• First Submitted: November 25, 2015
• First Submitted That Met QC Criteria: December 2, 2015
• First Posted (ESTIMATE): December 3, 2015

Study Record Updates

• Last Update Posted (ACTUAL): May 12, 2021
• Last Update Submitted That Met QC Criteria: May 10, 2021
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenocarcinoma; Adenocarcinoma of Lung
• Other Study ID Numbers: HenanCH003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: terminated as the slow enrollment