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

• ClinicalTrials.gov Identifier: NCT02621333
• Recruitment Status: Terminated
• First Posted: December 3, 2015
• Last Update Posted: May 12, 2021
• Sponsor: Henan Cancer Hospital
• Collaborators: Henan Provincial People's Hospital; Hebei Medical University Fourth Hospital; Shanxi Dayi Hospital; Tangshan People's Hospital; 150th Hospital of PLA; First Affiliated Hospital of Nanyang Medical College; Nanyang Central Hospital; First People's Hospital of Shangqiu; Anyang Regional Hospital; Puyang Oilfield General Hospital; Shenma Medical Group General Hospital; Jiaozuo Tumor Hospital; The 152th Central Hospital of PLA; Xinyang Central Hospital
• Information provided by (Responsible Party): Quanli Gao, Henan Cancer Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Lung Adenocarcinoma	Biological: CIK; Drug: chemotherapy	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 280 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 2015
• Actual Primary Completion Date: September 2018
• Actual Study Completion Date: September 2018

Arms and Interventions

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 Name: 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 Name: 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 Name: platinum combined doublets

Outcome Measures

Primary Outcome Measures :

1. overall survival time [ Time Frame: from the day of randomization to the day of death, up to 36 months ]
   overall survival time aims at from date of randomization until the date of death from any cause, up to 36 months

Secondary Outcome Measures :

1. time to progression [ Time Frame: from the day of randomization to the day of first detecting progression, up to 24 months ]
   time to progression points to from date of randomization until the date of first documented progression, up to 24 months
2. objective response rate [ Time Frame: one year ]
   the partion of overall remission in total proportion

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

China, Henan

Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university

ZhengZhou, Henan, China, 450008

Sponsors and Collaborators

Henan Cancer Hospital

Henan Provincial People's Hospital

Hebei Medical University Fourth Hospital

Shanxi Dayi Hospital

Tangshan People's Hospital

150th Hospital of PLA

First Affiliated Hospital of Nanyang Medical College

Nanyang Central Hospital

First People's Hospital of Shangqiu

Anyang Regional Hospital

Puyang Oilfield General Hospital

Shenma Medical Group General Hospital

Jiaozuo Tumor Hospital

The 152th Central Hospital of PLA

Xinyang Central Hospital

Investigators

• Study Director: Quanli Gao, M.D.; Henan Cancer Hospital

More Information

Publications of Results:

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. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Quanli Gao, director, Henan Cancer Hospital
• ClinicalTrials.gov Identifier: NCT02621333
• Other Study ID Numbers: HenanCH003
• First Posted: December 3, 2015
• Last Update Posted: May 12, 2021
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: terminated as the slow enrollment

Additional relevant MeSH terms:

Adenocarcinoma; Adenocarcinoma of Lung; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site