UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A biomarker analysis of plasma and tumor DNA in afatinib-treatedpatients with EGFR mutation-positive advanced adenocarcinoma of the lung.
Title of the study (Brief title)	Afatinib I I S
Region	Japan

Condition
Condition	adenocarcinoma of the lung
Classification by specialty	Pneumology Laboratory medicine
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	1.To investigate gene mutation and expression level as a biomarker related with the resistance to afatinib in EGFR gene mutation-positive pulmonary adenocarcinoma using a tumor tissue and a peripheral circulatory free DNA. 2.To investigate clinical benefit of peripheral circulatory free DNA.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	A detection of a biomarker about afatinib tolerance
Key secondary outcomes	1.Progression Free Survival 2.Time to Systemic PD 3.Response rate 4.Safety

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Afatinib40mg/day:oral daily
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1) Patients with pulmonary adenocarcinoma with a histological diagnosis and cytodiagnosis. 2) Patients with EGFR gene mutation(exon 19 deletion mutation or L858R mutation in exon 21)within 1 year before enrollment. 3)Patients whose tumor specimen can be submitted. 4)Patients with pathologically confirmed diagnosis of stage IIIB(not amenable for curative intent local radiotherapy)/IV (recurrent or metastatic)adenocarcinoma of the lung. 5) Patients with no treatment of EGFR-TKI. 6) Patients that 2 wks pass from the last dosage of the anticancer drug in the case of systemic chemotherapy. 7) Patients with more than 20 years old on the enrollment day. 8) Patients with ECOG PS 0 or 1. 9) Patients harboring a more than one measurable lesion. 10) Patient whose latest level of laboratory test within 14 days before enrollment meets all following categories (the examination of the same date two weeks before the registration day is permitted). (1) Neutrophil >= 1,500/mm3 (2) Hemoglobin >= 9.0 g/dL(A blood transfusion is not enforced within 14 days of the examination before enrollment) (3) Platelet >= 10X104/ mm3 (4) Total bilirubin <= 1.5 mg/dl (5) AST(GOT)<= 100 (6) ALT(GPT)<= 100 (7) Serum creatinine <= 2.0 mg/dl (8) SpO2 >= 92%. In case of SpO2 < 92%, PaO2 >= 60 torr is eligible. 11) Patients providing written informed consent.
Key exclusion criteria	1) Patients with active double cancer 2)Patients with interstitial pneumonia confirmed by chest CT. 3)Patient with neurologic symptom caused by non-treated brain metastasis 4) Patients with either superior vena cava syndrome, pericardial effusion, pleural effusion or ascites >= Grade 3. 5) Patients with an operation with the systemic anesthesia within 28 days before enrollment. 6)Patient with a palliative radiotherapy for the metastatic focus except the chest (including gamma knife treatment for the brain metastatic focus) within 7 days before enrollment (the irradiation of the same day 2 weeks ago is permitted as enrollment day as day0). 7) Patient with a radiation exposure to the chest or mediastinum within 14 days before enrollment (the irradiation of the same day 2 weeks ago is permitted as enrollment day as day0). 8)Patients with complication with mental disease or a mind symptom, and are judged to have difficulty in participation in the study. 9) Patient with positive HBs antigen. 10) Patient having a serious infection to need systemic treatment. 11)Any other patients who are regarded as unsuitable for this study by the investigators.
Target sample size	30

Research contact person
Name of lead principal investigator	Isamu Okamoto
Organization	Kyushu University Hospital
Division name	Research Institute for Disease of the Chest / Center for Clinical and Translational Research
Address	3-1-1 Maidashi ,Higashi-ku,Fukuoka,
TEL	092-642-5378
Email	okamotoi@kokyu.med.kyushu-u.ac.jp

Public contact
Name of contact person	Eiji Iwama
Organization	Graduate School of Medical Sciences, Kyushu University
Division name	Faculty of Medical Sciences, Department of Comprehensive Clinical Oncology
Address	3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan, 812-8582
TEL	092-642-5378
Homepage URL
Email	iwama@kokyu.med.kyushu-u.ac.jp

Sponsor
Institute	Clinical Research Support Center Kyushu
Institute
Department

Funding Source
Organization	Nippon Boehringer Ingelheim Co., Ltd.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2014 Year 05 Month 07 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2014 Year 04 Month 17 Day
Anticipated trial start date	2014 Year 05 Month 07 Day
Last follow-up date	2017 Year 11 Month 30 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2014 Year 04 Month 25 Day
Last modified on	2018 Year 04 Month 27 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000016105