UMIN-CTR Clinical Trial

Basic information
Public title	Effect of drug metabolizing enzyme gene polymorphism on selective estrogen receptor modulator pharmacokinetics in breast cancer (JBCRG-12)
Acronym	JBCRG-12 (Pharmacokinetics-pharmacogenomics study in breast cancer endocrine treatment)
Scientific Title	Effect of drug metabolizing enzyme gene polymorphism on selective estrogen receptor modulator pharmacokinetics in breast cancer (JBCRG-12)
Scientific Title:Acronym	JBCRG-12 (Pharmacokinetics-pharmacogenomics study in breast cancer endocrine treatment)
Region	Japan

Condition
Condition	Breast cancer
Classification by specialty	Hematology and clinical oncology Breast surgery
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	Investigate the correlation between CYP2D6 gene polymorphism and pharmacokinetics of tamoxifen or toremifen. Correlations with adverse event or clinical efficacy will be analyzed, too.
Basic objectives2	Pharmacokinetics
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Not applicable

Assessment
Primary outcomes	CYP2D6 gene polymorphism Pharmacokinetics of tamoxifen and its active metabolites or toremifen and its active metabolites
Key secondary outcomes	Adverse event Drug efficacy

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	Prevention
Type of intervention	Maneuver
Interventions/Control_1	Blood test
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	Not applicable
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	Breast cancer patients who are taking either tamoxifen or toremifen
Key exclusion criteria	None
Target sample size	200

Research contact person
Name of lead principal investigator	1st name Hiroshi Middle name Last name Ishiguro
Organization	Graduate School of Medicine Kyoto University
Division name	Department of Target Therapy Oncology
Zip code	606-8507
Address	54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, Japan
TEL	075-751-4950
Email	hkkishi@kuhp.kyoto-u.ac.jp

Public contact
Name of contact person	1st name Hiroshi Middle name Last name Ishiguro
Organization	Graduate School of Medicine Kyoto University
Division name	Department of Target Therapy Oncology
Zip code	606-8507
Address	54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, Japan
TEL	075-751-4950
Homepage URL	https://www.jbcrg.jp/
Email	hkkishi@kuhp.kyoto-u.ac.jp

Sponsor
Institute	JBCRG(Japan Breast Cancer Research Group)
Institute
Department

Funding Source
Organization	JBCRG(Japan Breast Cancer Research Group)
Organization
Division
Category of Funding Organization	Non profit foundation
Nationality of Funding Organization

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

IRB Contact (For public release)
Organization	JBCRG
Address	9-4 Nihonbashikoamicho, Chuo-ku, Tokyo, Japan
Tel	03-6264-8873
Email	office@jbcrg.jp

Secondary IDs
Secondary IDs	YES
Study ID_1	JBCRG-12
Org. issuing International ID_1	Japan Breast Cancer Research Group
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	京都大学医学部附属病院（京都府） 群馬県立がんセンター（群馬県） 都立駒込病院（東京都） 兵庫県立がんセンター（兵庫県） 九州がんセンター（福岡県） 新潟県立がんセンター（新潟県） 筑波大学附属病院（茨城県） 広島大学病院（広島県） 熊本大学医学部附属病院（熊本県） 彦根市立病院（滋賀県） 愛知県がんセンター中央病院（愛知県）

Other administrative information
Date of disclosure of the study information	2009 Year 02 Month 01 Day

Related information
URL releasing protocol	https://upload.umin.ac.jp/cgi-bin/ctr/ctr_up_reg_f5.cgi
Publication of results	Published

Result
URL related to results and publications	https://link.springer.com/article/10.1007%2Fs12282-019-00952-9
Number of participants that the trial has enrolled	273
Results	The CYP2D6 genotype was the major determinant for TAM activity (p < 0.01). Smoking status (p = 0.07) and the CYP2C19 phenotype (p = 0.07), but not the CYP2D6 genotype (p = 0.61), showed marginally significant effects on TOR activity.
Results date posted	2021 Year 08 Month 06 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results	2019 Year 02 Month 07 Day
Baseline Characteristics	Age (Median): 50years old Weight (Median): 52.9kg History of smoking+: 5.5% Anti-estrogen used TAM 20mg 66.7% TOR40mg 22.3mg TOR 120mg 11.0% CYP inhibitor use 　2D6 inhibitor:　1.1% 　3A4 inhibitor:　4.4% 　both:　5.1% 　none: 89.5%
Participant flow	Breast cancer patients taking either TAM or TOR were enrolled. Pharmacogenomics (PGx) analysis for CYP2D6, CYP2C19, and ABCC2 (MRP2) was conducted.
Adverse events	Hot flush Grade 1: 29.7% Grade 2: 9.9% Grade 3: 0.4%
Outcome measures	Polymorphism of CYP2D6, CYP2C19 and ABCC2 Pharmacokinetics of TAM and TOR
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2009 Year 01 Month 19 Day
Date of IRB
Anticipated trial start date	2009 Year 02 Month 01 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2009 Year 01 Month 28 Day
Last modified on	2021 Year 08 Month 13 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000002013