UMIN-CTR Clinical Trial

Basic information
Public title	Tamoxifen Response by CYP2D6 Genotype-Based Treatment in Patients with Metastatic or Recurrent Breast Cancer
Acronym	TARGET-1 study
Scientific Title	Tamoxifen Response by CYP2D6 Genotype-Based Treatment in Patients with Metastatic or Recurrent Breast Cancer
Scientific Title:Acronym	TARGET-1 study
Region	Japan

Condition
Condition	Hormone receptor-positive metastatic or recurrent breast cancer
Classification by specialty	Hematology and clinical oncology Breast surgery
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	This phase II trial is studying to evaluate an application of tamoxifen dose adjustment based on CYP2D6 genotypes for treatment with patients in hormone receptor-positive metastatic or recurrent breast cancer.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Progression free rate at 6 months after the patient randomization
Key secondary outcomes	1) Response rate (CR+PR) 2) Clinical benefit (CR+PR + SD for longer than 6 months) 3) Relationship between trough levels of tamoxifen, endoxifen, 4-hydroxytamoxifen and N-desmethyltamoxifen at steady state and efficacy and/or adverse reactions 4) Exploration of factors affecting the response

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Dose comparison
Stratification	YES
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	3
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	CYP2D6 wt/wt : 20mg/day for 24 weeks
Interventions/Control_2	CYP2D6 wt/V or V/V : 20mg/day for 24 weeks
Interventions/Control_3	CYP2D6 wt/V or V/V : 40mg/day for 24 weeks
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	Female
Key inclusion criteria	1) Metastatic or recurrent breast cancer 2) Estrogen-receptor positive 3) Patients who are planning to undergo tamoxifen treatment for the primary treatment breast cancer 4) Patients having measurable target lesions 5) ECOG performance status (PS) 0-1 6) Patients having no severely impaired main organs and marrow 7) Patients who are expected to survive more than 6 months after the first registration day 8) Patients must receive an adequate explanation of the trial before enrollment and sign a written informed consent document
Key exclusion criteria	1) HER2 status positive 2) Prior endocrine therapy for recurrent or metastatic disease 3) Prior chemotherapy for recurrent or metastatic disease 4) Patients having active double cancer 5) Patients having CNS metastasis 6) Patients receiving continuous systemic administration of steroids 7) Patients receiving prohibited concomitant medications 8) Patients having difficulty to enroll to the study for psychiatric reasons 9) Patients who are pregnant (or might be pregnant), nursing, or those who will not use contraceptive methods 10) Other cases determined as being unsuitable by the investigators
Target sample size	180

Research contact person
Name of lead principal investigator	1st name Yusuke Middle name Last name Tanigawara
Organization	Keio University, School of Medicine
Division name	Department of Clinical Pharmacokinetics and Pharmacodynamics
Zip code	160-8582
Address	35 Shinanomachi, Shinjuku-ku, Tokyo, JAPAN
TEL	03-5363-3847
Email	tanigawara@a7.keio.jp

Public contact
Name of contact person	1st name Kenji Middle name Last name Tamura
Organization	National Cancer Center Hospital
Division name	Department of Breast and Medical Oncology
Zip code	104-0045
Address	5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, JAPAN
TEL	03-3542-2511
Homepage URL
Email	ketamura@ncc.go.jp

Sponsor
Institute	National Cancer Center Hospital
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization	JAPAN

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

IRB Contact (For public release)
Organization	RIKEN
Address	1-7-22 Suehirocho, Tsurumi-ku, Yokohama
Tel	045-503-9111
Email	yokohama-web@riken.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

Other administrative information
Date of disclosure of the study information	2012 Year 10 Month 20 Day

Related information
URL releasing protocol	doi: 10.1200/JCO.19.01412.
Publication of results	Published

Result
URL related to results and publications	doi: 10.1200/JCO.19.01412.
Number of participants that the trial has enrolled	186
Results	Between December 2012 and July 2016, 186 patients were enrolled in Japan.
Results date posted	2022 Year 07 Month 06 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	Of 184 evaluable patients, 136 carried wt/V or V/V, and 48 carried wt/wt.
Participant flow	136 with wt/V or V/V were randomly assigned to either the ID arm (n = 70) or RD arm (n = 66), and 48 with wt/wt were not randomly assigned and continued taking 20 mg of tamoxifen daily.
Adverse events	The incidence of adverse events, including hot flush and hypertriglyceridemia (common tamoxifen-related adverse events), did not differ significantly between the ID and RD arms.
Outcome measures	In patients with wt/V or V/V, the PFS rates at 6 months did not differ significantly between the ID arm (67.6%; 95% CI,56.5% to 78.8%) and the RD arm (66.7%; 95% CI, 55.0% to 78.3%).
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2012 Year 09 Month 27 Day
Date of IRB	2012 Year 12 Month 05 Day
Anticipated trial start date	2016 Year 09 Month 14 Day
Last follow-up date	2017 Year 03 Month 31 Day
Date of closure to data entry	2017 Year 05 Month 31 Day
Date trial data considered complete	2017 Year 06 Month 30 Day
Date analysis concluded	2017 Year 12 Month 31 Day

Other
Other related information

Management information
Registered date	2012 Year 10 Month 20 Day
Last modified on	2022 Year 07 Month 06 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000010735