Clinical trial NCT02621333: Chemotherapy Combined Autologous Cytokine-induced Killer Cells in Naive Stage IV 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lung Adenocarcinoma
Lead sponsor: Henan Cancer Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Henan Provincial People's Hospital
name: Hebei Medical University Fourth Hospital
name: Shanxi Dayi Hospital
name: Tangshan People's Hospital
name: 150th Hospital of PLA
name: First Affiliated Hospital of Nanyang Medical College
name: Nanyang Central Hospital
name: First People's Hospital of Shangqiu
name: Anyang Regional Hospital
name: Puyang Oilfield General Hospital
name: Shenma Medical Group General Hospital
name: Jiaozuo Tumor Hospital
name: The 152th Central Hospital of PLA
name: Xinyang Central Hospital
First posted: 2015-12-03
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: overall survival time
timeFrame: from the day of randomization to the day of death, up to 36 months
Secondary outcomes:
measure: time to progression
timeFrame: from the day of randomization to the day of first detecting progression, up to 24 months
measure: objective response rate
timeFrame: one year
Other outcomes:
Locations:
city: ZhengZhou
country: China
facility: Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university
state: Henan
Study officials:
affiliation: Henan Cancer Hospital
name: Quanli Gao, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.