UMIN-CTR Clinical Trial

Basic information
Public title	Real world evidence of PD-L1, TMB prevalence and efficacy of 1st line chemotherapy in these high or low population for stage IV urothelial cancer
Acronym	YODO study Real world evidence of PD-L1 prevalence and efficacy of 1st line chemotherapy for stage IV urothelial cancer
Scientific Title	Real world evidence of PD-L1, TMB prevalence and efficacy of 1st line chemotherapy in these high or low population for stage IV urothelial cancer
Scientific Title:Acronym	YODO study Real world evidence of PD-L1 prevalence and efficacy of 1st line chemotherapy for stage IV urothelial cancer
Region	Japan

Condition
Condition	Stage IV urothelial cancer
Classification by specialty	Urology
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	To evaluate prevalence of PD-L1 expression on tumor cell and immune cell in stage IV UC patients in real world setting.
Basic objectives2	Others
Basic objectives -Others	Secondary objectives 1.To evaluate prevalence of TMB in tissue tumor or immune cell in stage IV UC patients in real world setting. 2.To assess OS, PFS from start of 1st line treatment in stage IV. 3.To investigate treatment pattern in stage IV UC patients. Exploratory Objective(s) 1.To evaluate cancer-immune phenotype of stage IV UC patients in real world setting. 2.To evaluate OS and PFS from start of 1st line treatment in stage IV in patients sub populations [Sub populations] PD-L1 high or low, negative population PD-L1 expression on tumor tissue or immune cell; 0, 10, 25, 50, 75, 100% TMB high or low population Cancer-immune phenotype; Immune-desert / Immune-excluded / Inflamed others 3.To evaluate the presence of gene mutations in primary tumor tissues in stage IV UC patients
Trial characteristics_1	Others
Trial characteristics_2	Others
Developmental phase	Not applicable

Assessment
Primary outcomes	PD-L1 High or Low/ Negative
Key secondary outcomes	Secondary Endpoints 1.TMB levels, TMB high or Low/ Negative 2.Median OS and OS rate at 12 months, 18 months and 24 months from start of 1st line treatment in stage IV. Median PFS and PFS rate at 6 months, 12 months and 18 months from start of 1st line treatment in stage IV. 3.Treatment patterns from 1st line treatment to 3rd line treatment in stage IV. Exploratory Endpoints 1.Cancer immune phenotype: immune-desert, immune-excluded or inflamed 2.Median OS and OS rate at 12 months, 18 months and 24 months from start of 1st line treatment in stage IV in patients sub populations. Median PFS and PFS rate at 6 months, 12 months and 18 months from start of 1st line treatment in stage IV in patients sub populations. [Sub populations] PD-L1 high or low/negative population PD-L1 expression; 0, 10, 25, 50, 75, 100% TMB high or low population Cancer immune phenotype; Immune-desert, immune-excluded or inflamed 3.Patients number and ratio in each gene mutations in primary tumor tissues analysed by NGS

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. Age > 20, Japanese men and women. 2. Patients who have started at least 1 cycle of chemotherapy. 3.Patients who provided informed consent by appropriate methods. In dead case, optout will be applicable. 4.Patients who are diagnosed as stage IV (AJCC, 7th edition) UC between January 1st in 2017 and December 31st in 2018. 5. Patients who have FFPE primary tumor sample collected after January 1st in 2017. The sample should be collected before any therapies including 1st line treatment in stage IV and therapies in stage III and other stages. It is preferable to also send a sample taken before neoajuvant therapy, even if it was taken before 1st Jan 2017.
Key exclusion criteria	1.Patients who are prior exposure to immune-mediated therapy as 1st line treatment in stage IV.
Target sample size	150

Research contact person
Name of lead principal investigator	1st name Masahisa Middle name Last name Jinushi
Organization	AstraZeneca K.K.
Division name	Medical, Oncology
Zip code	530-0011
Address	Grand Front Osaka Tower B 3-1, Ofuka-cho, Kita-ku, Osaka 530-0011
TEL	06-7711-3044
Email	Masahisa.jinushi@astrazeneca.com

Public contact
Name of contact person	1st name Mika Middle name Last name Kanno
Organization	Linical Co.,Ltd.
Division name	Contract Medical Affairs Unit, Clinical Trial Operations
Zip code	105-0021
Address	1-9-2 Higashi-shimbashi, Minato-ku, Tokyo, 105-0021, Japan
TEL	03-6215-8005
Homepage URL
Email	kanno-mika@linical.co.jp

Sponsor
Institute	AstraZeneca K.K.
Institute
Department

Funding Source
Organization	AstraZeneca K.K.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	Linical Co.,Ltd.
Name of secondary funder(s)

IRB Contact (For public release)
Organization	N/A
Address	N/A
Tel	N/A
Email	N/A

Secondary IDs
Secondary IDs	YES
Study ID_1	D419BR00014
Org. issuing International ID_1	AstraZeneca K.K.
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions

Institutions

国家公務員共済組合連合会　横須賀共済病院（神奈川県）、筑波大学附属病院（茨城県）、奈良県立医科大学附属病院（奈良県）、弘前大学医学部附属病院（青森県）、浜松医科大学医学部附属病院（静岡県）、国立大学法人高知大学医学部附属病院（高知県）、独立行政法人国立病院機構　北海道がんセンター（北海道）、社会福祉法人　函館厚生院　函館五稜郭病院（北海道）、国立大学法人山口大学医学部附属病院（山口県）、地方独立行政法人神戸市民病院機構　神戸市立医療センター中央市民病院（兵庫県）、国立研究開発法人国立がん研究センター中央病院（東京都）、国立大学法人 岐阜大学医学部附属病院（岐阜県）、国立大学法人愛媛大学医学部附属病院（愛媛県）、鳥取大学医学部附属病院（鳥取県）、長崎大学病院（長崎県）、国立大学法人宮崎大学医学部附属病院（宮崎県）、大阪医科大学附属病院（大阪府）、国立大学法人東北大学東北大学病院（宮城県）、医療法人 原三信病院（福岡県）、独立行政法人労働者健康安全機構　大阪労災病院（大阪府）、公益財団法人大原記念倉敷中央医療機構 倉敷中央病院（岡山県）

Other administrative information
Date of disclosure of the study information	2019 Year 09 Month 01 Day

Related information
URL releasing protocol	Unpublished
Publication of results	Unpublished

Result
URL related to results and publications	Unpublished
Number of participants that the trial has enrolled	143
Results	By performing validated assay techniques on the FFPE samples, including Ventana PD-L1 (SP263) assay and NGS, PD-L1 expression, histological classification, cancer-immune phenotype, and TMB could be determined. Based on these data, prevalence of the immunogenic biomarkers including PD-L1 expression, TMB and OS, PFS from start of first-line treatment for Stage IV urothelial cancer was assessed.
Results date posted	2021 Year 03 Month 31 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	his was a study of real-world evidence to evaluate the prevalence of PD-L1, TMB and cancer-immune phenotype as well as the correlation between these immunogenic biomarkers and clinical manifestation including prognosis and treatment regimens in 143 eligible patients with Stage IV urothelial cancer and a mean (SD) age of 71.7 (9.84) years.
Participant flow	Patients who provided informed consent by appropriate methods were included. In dead case or moving out case, optout was applicable according to the rule of EC.
Adverse events	Not applicable
Outcome measures	Unpublished
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2019 Year 07 Month 10 Day
Date of IRB	2019 Year 09 Month 25 Day
Anticipated trial start date	2019 Year 09 Month 01 Day
Last follow-up date	2020 Year 03 Month 26 Day
Date of closure to data entry	2020 Year 04 Month 30 Day
Date trial data considered complete	2020 Year 10 Month 26 Day
Date analysis concluded	2021 Year 01 Month 31 Day

Other

Other related information

Study Design This study is a multi-center, non-interventional study. Patients' background, treatment pattern, treatment outcome, efficacy will be collected from medical records in Stage IV UC patients. Archived patient's formalin-fixed paraffin-embedded (FFPE) primary tumor samples will be collected from each site and conduct PD-L1 assay, classification of histology and cancer-immune phenotype and next generation sequencer (NGS) assay for TMB. Based on these data, prevalence of PD-L1 expression, TMB and OS, PFS from start of 1st line treatment in stage IV will be assessed. In this study, 150 patients will be enrolled from 30 sites at max in Japan. The patients will be enrolled continuously from the 1st patient who is enrolled in this study until target number of patients in each site. The patient enrolment will start from September 2019, and will end May 2020.

Management information
Registered date	2019 Year 08 Month 19 Day
Last modified on	2021 Year 03 Month 31 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000043026