UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Afatinib Plus Bevacizumab After Acquired Resistance to EGFR-TKI in EGFR-mutant NSCLC
Title of the study (Brief title)	Afatinib Plus Bevacizumab After Acquired Resistance to EGFR-TKI
Region	Japan

Condition
Condition	Non-small cell lung cancer
Classification by specialty	Medicine in general Pneumology Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	To investigate the efficacy and safety of Afatinib plus Bevacizumab in patients with EGFR-mutant NSCLC after acquired resistance to EGFR-TKI
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase II

Assessment
Primary outcomes	Response rate
Key secondary outcomes	Progression-free survival Disease control rate Overall survival Safety

Base
Study type

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	Afatinib is prescribed at 30 mg/day everyday, and bevacizumab is injected at 15 mg/kg every 3 weeks until progressive disease. If possible, rebiopsy is performed to confirm T790M status. To evaluate the safety, the traetment of afatinib should be administered at 30 mg/day in initial 6 cases only at institute of Biomedical Reseach and Innovation. After the treatment of this 6 cases, Data and Safety Monitoring Committee will judge the trial proceeding, based on safety results of this 6 cases.
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)Histological or cytological proven NSCLC (except squamous hislotogy) 2)EGFR mutation positive 3)After acquired resistance to EGFR-TKI (briefly, SD>6 months, defined by Jackman criteria) 4)Interval of radiation therapy: 4 weeks after thoracic RT and 1 week after non-thoracic RT 5)Age: over 20 6)ECOG PS: 0-2 7)Adequate organ functions judged by laboratory tests 8)Life expectancy: over 3 months 9)Written informed consent
Key exclusion criteria	1)Obvious interstitial pneumonia or pulmonary fibrosis by chest CT 2)History of severe allergic reaction 3)Complications such as severe infection or severe comobidities 4)Uncontrolled pleural or pericardial effusion 5)Clinically significant heart disease 6)Uncontrolled hypertension 7)Uncontrolled diabate 8)Active multiple cancer 9)Squamous histology 10)Aparent invasion of main vessels 11)Clinically significant phycological problem 12)History of significant hemoptysis or respiratory bleeding 13)History of GI perfolation 14)non-curable bone fracture or severe injury 15)Planning surgery 16)Significant lung cavitation 17)Bleeding tendency 18)Uncontrolled thromboembolism 19)Prior therapy of EGFR-TKI+bevacizumab 20)History of Afatinib administration 21)Pregnancy 22)Inadequate patients whom physitians considered
Target sample size	32

Research contact person
Name of lead principal investigator	Nobuyuki Katakami
Organization	Institute of Biomedical Research and Innovation
Division name	Division of Integrated Oncology
Address	2-2, Minatojima-minamimachi, Chuo-ku, Kobe
TEL	078-304-5200
Email	katakami@fbri.org

Public contact
Name of contact person	Akito Hata
Organization	Institute of Biomedical Research and Innovation
Division name	Division of Integrated Oncology
Address	2-2, Minatojima-minamimachi, Chuo-ku, Kobe
TEL	078-304-5200
Homepage URL
Email	a-hata@fbri.org

Sponsor
Institute	Foundation for Biomedical Research and Innovation
Institute
Department

Funding Source
Organization	Foundation for Biomedical Research and Innovation
Organization
Division
Category of Funding Organization	Non profit foundation
Nationality of Funding Organization

Other related organizations
Co-sponsor	HANSHIN Oncology Group
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	大阪府立成人病センター呼吸器内科（大阪府）京都桂病院呼吸器内科（京都府）、倉敷中央病院呼吸器内科（岡山県）、神戸市立医療センター中央市民病院呼吸器内科（兵庫県）、神戸市立医療センター西市民病院呼吸器内科（兵庫県）、神戸大学医学部附属病院呼吸器内科（兵庫県）、刀根山病院呼吸器腫瘍内科（大阪府）、先端医療センター総合腫瘍科（兵庫県）、兵庫県立がんセンター呼吸器内科（兵庫県）

Other administrative information
Date of disclosure of the study information	2014 Year 08 Month 01 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2014 Year 07 Month 22 Day
Anticipated trial start date	2014 Year 08 Month 01 Day
Last follow-up date	2017 Year 12 Month 01 Day
Date of closure to data entry	2017 Year 12 Month 01 Day
Date trial data considered complete	2017 Year 12 Month 01 Day
Date analysis concluded	2017 Year 12 Month 01 Day

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

Management information
Registered date	2014 Year 07 Month 30 Day
Last modified on	2017 Year 12 Month 24 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017092