UMIN-CTR Clinical Trial

Basic information
Public title	Observational research to decide optimal dose of Afatinib in patients with primary lung adenocarcinoma harbouring the sensitive mutation of epidermal growth factor receptor (EGFR) by pharmacokinetic analyses
Acronym	Observational research to decide optimal dose of Afatinib by pharmacokinetic analyses
Scientific Title	Observational research to decide optimal dose of Afatinib in patients with primary lung adenocarcinoma harbouring the sensitive mutation of epidermal growth factor receptor (EGFR) by pharmacokinetic analyses
Scientific Title:Acronym	Observational research to decide optimal dose of Afatinib by pharmacokinetic analyses
Region	Japan

Condition
Condition	Patients have primary lung adenocarcinoma harbouring the sensitive mutation of epidermal growth factor receptor (EGFR)
Classification by specialty	Medicine in general Pneumology Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To seek optimal dose of Afatinib in patients with primary lung adenocarcinoma harbouring the sensitive mutation of EGFR by pharmacokinetic analyses
Basic objectives2	Others
Basic objectives -Others	To examine the relationship between the efficacy of Afatinib and the copy number of EGFR mutation
Trial characteristics_1	Exploratory
Trial characteristics_2	Others
Developmental phase	Not applicable

Assessment
Primary outcomes	To seek the pharmacological optimal dose of Afatinib in patients with primary lung adenocarcinoma harbouring the sensitive mutation of EGFR by pharmacokinetic analyses
Key secondary outcomes	To seek the clinical optimal dose of Afatinib: Progression free survival (PFS),Time to Treatment failure (TTF), Health states evaluation; time with toxicity more than Grade 2 (TOX-G2), 20% duration of TOX-G2 among PFS (20% TOX-G2; TOX20). To examine the relationship between the efficacy of Afatinib and the copy number of EGFR mutation

Base
Study type	Observational

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
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)Histologically or cytologically proven lung adenocarcinoma 2)Stage IIIB/IV(UICC ver.8) or recurrence after surgical treatment 3)Tumor has sensitive mutation for EGFR-TKI 4)Naive treatment of EGFR-TKI 5)Tumor has the evaluable lesion 6)Eastern Cooperative Oncology Group performance status of 0-2 7)Age; > or = 20 years and < 80 years 8) No history of thoracic irradiation 9)Adequate organ function, Adequate organ function Neutrocyte count; > or = 1,500/mm3 Hemoglobin concentration; > or = 10.0g/dl Platelet count; > or = 100,000/mm3 Total bilirubin level; < or = 2.0 mg/dl Aspartate aminotransferse and alanine aminotransferase levels; < or = 100 IU/L Creatinine clearance; > or = 30mL/min Or serum creatinine; < or = 1.5 mg/dl SpO2 at room air; > or = 70 torr at room air 10)Neither overt interstitial pneumonia nor overt lung fibrosis 11)Written informed consent
Key exclusion criteria	Exclusion criteria included: 1)Uncontrollable comorbid disease. 2)Symptomatic brain metastases 3)Active concomitant malignancy 4)Active infectious disease 5)Pregnant status or lactation 6)Acute or chronic diarrhea 7)Clinically active interstitial pneumonia 8)Acute myocardial ischemia within 3 months or unstable angina pectoris 9)Other ineligible status judged by medical oncologist
Target sample size	34

Research contact person
Name of lead principal investigator	1st name Yuichiro Middle name Last name Takeda
Organization	Center Hospital of the National Center for Global health and Medicine
Division name	Department of Respiratory Medicine / Laboratory Testing Department
Zip code	1628655
Address	National Center for Global Health and Medicine
TEL	+81332027181
Email	ytakeda@hosp.ncgm.go.jp

Public contact
Name of contact person	1st name Yuichiro Middle name Last name Takeda
Organization	National Center for Global Health and Medicine
Division name	Department of Respiratory Medicine / Laboratory Testing Department
Zip code	1628655
Address	National Center for Global Health and Medicine
TEL	+81332027181
Homepage URL
Email	ytakeda@hosp.ncgm.go.jp

Sponsor
Institute	Department of Respiratory Medicine in the Center Hospital of the National Center for Global health and Medicine
Institute
Department

Funding Source
Organization	Research funding of the Department of Respiratory Medicine in the Center Hospital of the National Center for Global health and Medicine
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization	not applicable

Other related organizations
Co-sponsor	Department of drug metabolism and disposition Meiji pharmaceutical university
Name of secondary funder(s)	None

IRB Contact (For public release)
Organization	The institutional review board for clinical research
Address	1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
Tel	+81332027181
Email	rinrijm@hosp.ncgm.go.jp

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	国立国際医療研究センター病院（東京都）

Other administrative information
Date of disclosure of the study information	2018 Year 08 Month 01 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled	1
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Terminated
Date of protocol fixation	2018 Year 06 Month 17 Day
Date of IRB	2018 Year 07 Month 06 Day
Anticipated trial start date	2018 Year 10 Month 30 Day
Last follow-up date	2022 Year 03 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other

Other related information

According to the post hoc analyses from two phase III trial on afatinib, dose reduction led to decreases in the incidence of drug-related toxicities, and was more likely in patients with higher afatinib plasma concentrations. Patients who dose reduced to 30 mg had geometric mean afatinib plasma concentrations of 23.3 ng/ml, versus 22.8 ng/ml in patients who remained on 40 mg. The median PFS was similar in patients who dose reduced versus those who did not. Therefore, 20 mg to 40 mg daily dose of afatinib is clinically used according to weight, performance status, or comorbidity of patients. Due to significant delays in enrollment, the study was terminated as of March 31, 2022.

Management information
Registered date	2018 Year 07 Month 28 Day
Last modified on	2022 Year 05 Month 28 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000038257