UMIN-CTR Clinical Trial

Public title

An Exploratory Study a) using gene expression analysis to assess the Predictability of Resistance to Hormone Therapy and Chemotherapy sensitivity in Luminal Breast Cancer Patients who have a treatment history of CDK4/6 Inhibition and b) investigating patients with luminal or triple negative breast cancer showing FGF - FGFR Mutation/Amplification detected using FoundationOne Comprehensive Gene Expression Analysis

Acronym

JBCRG-C07-A1(REIWA2 study)

Scientific Title

An Exploratory Study a) using gene expression analysis to assess the Predictability of Resistance to Hormone Therapy and Chemotherapy sensitivity in Luminal Breast Cancer Patients who have a treatment history of CDK4/6 Inhibition and b) investigating patients with luminal or triple negative breast cancer showing FGF - FGFR Mutation/Amplification detected using FoundationOne Comprehensive Gene Expression Analysis

Scientific Title:Acronym

JBCRG-C07-A1(REIWA2 study)

Region

Japan

Condition

Patients with stage IV or recurrent breast cancer who have distant metastases at registration

Classification by specialty

Hematology and clinical oncology

Breast surgery

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

To determine whether the FoundationOne results, EMT score and the IO subtype can be used to evaluate the changes in the biological malignancy of tumors after treatment with CDK4/6 inhibitors, which are commonly used as a first and second-line treatment for recurrent luminal breast cancer. The study will also focus on the FGF/FGFR signaling pathway, which is activated after the use of CDK4/6 inhibitors and is considered a poor prognostic factor, in order to improve the biological understanding of this pathway and evaluate its correlation with the malignancy of luminal breast cancer. In addition, this study will examine whether diverse TNBC cases can be classified more clearly by evaluating the correlation of cases with molecular subtype and mutation.

Basic objectives2

Others

Basic objectives -Others

･To examine the changes in the expression levels of the FGF/FGFR genes and related genes before and after treatment with CDK4/6 inhibitors.
･To measure the EMT score and IO signature, and evaluate its ability to predict resistance to hormone therapy and the effect of chemotherapy through comparatively analysis.
･To examine the correlation between luminal breast cancer cases with confirmed FGFR mutation/amplification and cases that showed activation after CDK4/6 inhibitor treatment.
･To examine the correlation with molecular subtypes in TNBC cases with confirmed FGFR mutation/amplification.

Trial characteristics_1

Exploratory

Trial characteristics_2

Others

Developmental phase

Not applicable

Primary outcomes

･To examine the changes in the expression levels of the FGF/FGFR genes and related genes before and after treatment with CDK4/6 inhibitors.
･To examine the correlation between the expression of FGF/FGFR genes and related genes and the acquisition of resistance to drug treatments and prognosis in recurrent breast cancer after treatment with CDK4/6 inhibitors.
･To measure the EMT score and IO signature, and evaluate its ability to predict resistance to hormone therapy and the effect of chemotherapy through comparatively analysis with the clinical data.
･To evaluate the changes over time in the tumors through gene mutation analysis by FoundationOne and comprehensive gene expression analysis by RNA-seq in primary and recurrent lesions.
･To examine the correlation between luminal breast cancer cases with confirmed FGFR mutation/amplification and cases that showed activation after CDK4/6 inhibitor treatment.
･To examine the correlation with molecular subtypes in TNBC cases with confirmed FGFR mutation/amplification.

Key secondary outcomes

･The predictability of overall survival based on the EMT score.
･The predictability of overall survival based on the IO subtype.
･The primary and recurrence lesions will be compared by comprehensive gene expression analysis using RNA-seq data in an attempt to construct a novel biomarker for hormone resistance. Specifically, two-sample t-tests will be performed on the genes, and Ingenuity Pathway Analysis (IPA) will be performed for gene groups that show clear differences between the two types of lesions in the FDR0.01-0.05 range in order to elucidate their biological characteristics and determine whether they can be used as biomarkers.

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

(1)A patient in the Luminal cohort of the JBCRG07 observational study who has received treatment with CDK4/6 inhibitors and has undergone FoundationOne testing using a sample of the recurrent lesion after treatment and a patient in the Luminal cohort of the JBCRGC07 observational study who has undergone FoundationOne testing using a sample of the primary lesion, and has a sample of the recurrent lesion tissue taken after CDK4/6 inhibitor use in clinical practice that can be submitted.
(2)A patient in the TNBC cohort of the JBCRGC07 observational study with confirmed FGFR mutation/amplification.
(3)With or without participation in the JBCRG-C07 (REIWA) exam, a patient who can submit a pair sample of primary lesion and recurrent lesion before and after the use of CDK4 / 6 inhibitor.
(4)Cases for which written consent was obtained.

Key exclusion criteria

Cases deemed unsuitable for enrollment in this study by the Principal Investigators in each institution.

Target sample size

50

Name of lead principal investigator

1st name	Hiroko
Middle name
Last name	Masuda

Organization

Showa University

Division name

Department of breast surgical oncology

Zip code

142-8666

Address

1-5-8 Hatanodai Shinagawa-ku Tokyo,Japan

TEL

03-3784-8145

Email

hmasuda@med.showa-u.ac.jp

Name of contact person

1st name	Jun
Middle name
Last name	Fukase

Organization

Japan Breast Cancer Research Group (JBCRG)

Division name

Head office

Zip code

103-0016

Address

9-4-3F, Nihonbashikoamicho, Chuo-ku, Tokyo, Japan

TEL

03-6264-8873

Homepage URL

https://www.jbcrg.jp/

Email

office@jbcrg.jp

Institute

Japan Breast Cancer Research Group

Institute

Department

Personal name

Organization

Eisai Co., Ltd

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Showa University,
The University of Texas, MD Anderson Cancer Center.
Eisai Co.,Ltd

Name of secondary funder(s)

Organization

The ethics committee of Showa Univer sity school of Medicine

Address

1-5-8 Hatanodai Shinagawa-ku Tokyo, 142-8666

Tel

03-3784-8129

Email

m-rinri@ofc.showa-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

昭和大学（東京都）

Date of disclosure of the study information

2020

Year

10

Month

08

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Preinitiation

Date of protocol fixation

2020

Year

07

Month

16

Day

Date of IRB

2020

Year

09

Month

04

Day

Anticipated trial start date

2020

Year

10

Month

01

Day

Last follow-up date

2023

Year

06

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Study population:
Patients with stage IV or recurrent breast cancer who have distant metastases at registration. Especially focused on the patient who has received treatment with CDK4/6 inhibitors and has a sample of the recurrent lesion tissue taken after CDK4/6 inhibitor use in clinical practice that can be submitted.
Study duration: 3years
Objective:
To investigate changes in gene expression and gene mutations in tumor tissues before and after CDK4/6 inhibitors.
To examine the correlation between luminal breast cancer cases with confirmed FGFR mutation/amplification and cases that showed activation after CDK4/6 inhibitor treatment.
To examine the correlation with molecular subtypes in TNBC cases with confirmed FGFR mutation/amplification.

Registered date

2020

Year

10

Month

07

Day

Last modified on

2022

Year

02

Month

24

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047975