UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A multicenter, single arm phase 2 study to examine efficacy and cerebrospinal fluid transitivity of Osimertinib in leptomeningeal carcinomatosis (LMC) patients with non-small cell lung cancer harboring EGFR mutation
Title of the study (Brief title)	A phase 2 study of Osimertinib in LMC
Region	Japan North America

Condition
Condition	leptomeningeal carcinomatosis (LMC) patients with non-small cell lung cancer harboring EGFR mutation
Classification by specialty	Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	The purpose of this study is to evaluate efficacy and safety of Osimertinib in patients with lung cancer harboring EGFR mutation and metastasis to leptomeningeal carcinomatosis. This study is also conducted as a translational research to evaluate transitivity ofOsimertinib.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	1.Progression-free survival 2.Cerebrospinal fluid transitivity of osimertinib
Key secondary outcomes	1.ORR, DCR, OS, Safety profile 2.QOL Evaluation (EORTC QLQ-C30) 3.Change of neurological finding (Neurologogical exam) 4.CNS-RR,CNS-DCR,CNS-PFS 5.To explore a resistance factor

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	Osimertinib 80 mg/day
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 non-small cell lung cancer diagnosed histologically or cytologically (except SCC) 2.Patients with EGFR gene mutation 3.Patients who shows acquired EGFR-TKI resistance. Patients resistant to a regimen of EGFR-TKI + other drug can also be enrolled 4.Patients with documented EGFR exon 20 T790M mutation in any lesion when EGFR-TKI failure 5.Patients who are detected; -cytologically positive in CSF -EGFR gene mutation positive in CSF If both negative image can be confirmed as LMC with; 1:findings of thickened dura mater 2:image with exudation of contrast medium and attending doctor and clinical study officer as central review are confirmed. 6.For patients who received radiotherapy, time defined below has been passed from the last radiotherapy till their enrollment to the present study [1]Radiotherapy to lung field - over 4 weeks [2]Radiotherapy to whole brain or whole spinal marrow 7.Patients aged 20 years or more at informed consent 8.PS 0 to 2 9.Patients with maintaining sufficient functioning of major organs 10.Three weeks has passed since the last dose of cytotoxic anticancer drug 11.expected survival of not less than 3 months from start of the study treatment 12.Patients who were fully explained about the study and submitted written informed consent before enrollment 13.Desirably, patients have measurable or evaluable lesion according to definition in RECIST (Ver. 1.1), but this criterion is not mandatory.
Key exclusion criteria	1.Patients with interstitial pneumonia or lung fibrosis clearly demonstrated by chest CT 2.Patients with a history of serious drug allergy 3.Patients with any serious infectious disease or other serious concurrent medical condition (e.g., gastrointestinal hemorrhage) 4.Patients with high amount of or uncontrollable pleural effusion, ascites or pericardial effusion -If patients treat synechia with anticancer drugs who can participate in the study 5.Patients with any clinically problematic heart disease (e.g., uncontrollable arrhythmia/angina, cardiac failure) 6.Patients with uncontrollable diabetes mellitus concurrently 7.Patients with active double cancer 8.Patients with any clinically problematic psychiatric disorder 9.Patients with untreated fracture (except compression fracture associated with osteoporosis) or severe wound 10.Pregnant, lactating or possibly pregnant female patients, or patients reluctant to take an effective contraceptive measure 11.Patients have immuno-checkpoint inhibitor as previous treatment 12.Other patients who, in the opinion of the investigator, are not eligible for participation in the present study for any reason
Target sample size	15

Research contact person
Name of lead principal investigator	Nobuyuki Katakami
Organization	Institute of Biomedical Research and Innovation
Division name	Integrated Onclogy
Address	2-2, Minatojima-Minamimachi, Chuo-ku, Kobe
TEL	0783045200
Email	katakami@fbri.org

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

Sponsor
Institute	HANSHIN
Institute
Department

Funding Source
Organization	Astra Zeneca
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

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

Secondary IDs
Secondary IDs	YES
Study ID_1	HANSHIN0216
Org. issuing International ID_1	HANSHIN
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	明石医療センター 呼吸器内科 大阪府立成人病センター 呼吸器内科 金沢大学附属病院 がんセンター 関西医科大学附属病院 呼吸器腫瘍内科 京都桂病院 呼吸器内科 倉敷中央病院 呼吸器内科 神戸大学医学部附属病院 呼吸器内科 先端医療センター 総合腫瘍科 宝塚市立病院 腫瘍内科 刀根山病院 呼吸器腫瘍内科 兵庫県立がんセンター 呼吸器内科

Other administrative information
Date of disclosure of the study information	2016 Year 10 Month 01 Day

Progress
Recruitment status	Open public recruiting
Date of protocol fixation	2016 Year 08 Month 19 Day
Anticipated trial start date	2016 Year 10 Month 03 Day
Last follow-up date
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	2016 Year 08 Month 22 Day
Last modified on	2016 Year 10 Month 03 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000027314