UMIN-CTR Clinical Trial

Basic information
Public title	Prospective observational Study to explore the efficacy of Eribulin as 1st-line or 2nd-line chemotherapy in patients with HER2-negative hormone-resistant inoperable or recurrent metastatic breast cancer
Acronym	E-SPEC
Scientific Title	Prospective observational Study to explore the efficacy of Eribulin as 1st-line or 2nd-line chemotherapy in patients with HER2-negative hormone-resistant inoperable or recurrent metastatic breast cancer
Scientific Title:Acronym	E-SPEC
Region	Japan

Condition
Condition	HER2-negative hormone-resistant inoperable or recurrent metastatic breast cancer
Classification by specialty	Hematology and clinical oncology Breast surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	The purpose of this observational study is to investigate the efficacy of eribulin as the first or second line chemotherapy to prolong overall survival and to explore factors affecting the survival in patients with HER2-negative hormone-resistant inoperable or recurrent metastatic breast cancer who scheduled to receive the first or second line chemotherapy in clinical practice in Japan.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Not applicable

Assessment
Primary outcomes	Overall survival (OS) of the first line chemotherapy from starting date of the first line chemotherapy until death from any cause
Key secondary outcomes	1) Overall survival (OS) of the second and third line chemotherapy from starting date of each chemotherapy until death from any cause 2) Progression-free survival (PFS) of the first, second and third line chemotherapy 3) Post progression survival (PPS) of the first, second and third line chemotherapy 4) Time to treatment failure (TTF) of the first, second and third line chemotherapy 5) New metastasis-free survival (nMFS) of the first, second and third line chemotherapy 6) QALY (Japanese version of the EQ-5D-5L) 7) Serious adverse events

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	75 years-old >=
Gender	Female
Key inclusion criteria	1) Female patients with histologically or cytologically confirmed breast cancer. 2) Patients with inoperable or recurrent metastatic breast cancer regardless of the site and number, excluding symptomatic central nervous system metastases. 3) Patients with HER2-negative disease defined as ISH negative or IHC 0, 1+ or 2+ (Those with IHC 2+ are eligible, if the additional ISH test results are negative. Those are ineligible who are with any positive results of estrogen or progesterone receptor test on primary and recurrent lesion). 4) Patients who are resistant to hormone therapy. 5) Patients with indication for the first or second line chemotherapy in HER2-negative hormone-resistant inoperable or recurrent metastatic breast cancer who scheduled to receive the chemotherapy. 6) Patients with the Eastern Cooperative Oncology Group (ECOG) performance status score 0-3 at the time of enrollment. 7) Patients with adequate bone marrow and major organ function judged by the primary physician. 8) Patients who have signed written informed consent to participate in this study.
Key exclusion criteria	1) Patients with symptomatic metastasis in the central nervous system. 2) Patients with a previous history of hypersensitivity to any component of drugs administered in the treatment. 3) Patients considered inappropriate for the study participation judged by the primary physician.
Target sample size	360

Research contact person
Name of lead principal investigator	1st name Yuichiro Kikawa Middle name Last name Takeshi Kotake
Organization	Kobe city medical center general hospital Kyoto University Hospital
Division name	Department of Breast surgery
Zip code	6500047
Address	2-1-1, Minatojima minamimachi,chuo-ku,Kobe city,Hyogo 650-0047 Japan
TEL	0783024321
Email	u-1ro@kcho.jp

Public contact
Name of contact person	1st name Yuichiro Kikawa Middle name Last name Takeshi Kotake
Organization	Kobe city medical center general hospital Kyoto University Hospital
Division name	Department of Breast surgery
Zip code	6500047
Address	2-1-1, Minatojima minamimachi,chuo-ku,Kobe city,Hyogo 650-0047 Japan
TEL	0783024321
Homepage URL
Email	u-1ro@kcho.jp

Sponsor
Institute	Kyoto Breast Cancer Research Network (KBCRN)
Institute
Department

Funding Source
Organization	Eisai
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor	Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Kobe city medical center general hospital
Address	Kobe city medical center general hospital Kyoto University Hospital
Tel	0783024321
Email	u-1ro@kcho.jp

Secondary IDs
Secondary IDs	YES
Study ID_1	A001
Org. issuing International ID_1	Kyoto Breast Cancer Research Network (KBCRN)
Study ID_2	TRIBC1505
Org. issuing International ID_2	Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe
IND to MHLW

Institutions
Institutions	神戸市立医療センター中央市民病院（兵庫）、京都大学医学部附属病院（京都）、大阪赤十字病院（大阪）、天理よろず相談所病院（奈良）、北野病院（大阪）、日本赤十字社和歌山医療センター（和歌山）

Other administrative information
Date of disclosure of the study information	2015 Year 07 Month 06 Day

Related information
URL releasing protocol	none
Publication of results	Published

Result
URL related to results and publications	https://pubmed.ncbi.nlm.nih.gov/35460066/
Number of participants that the trial has enrolled	180
Results	Among 201 patients enrolled, 180 were included in the final analysis. Eribulin was administered as first- and second-line chemotherapy to 46 (26.6%) and 70 (47.9%) patients, respectively. Median OS1 and OS2 were 2.25 (95% CI 1.07-2.68) and 1.75 (95% CI, 1.28-2.45) years for first- and second-line eribulin, respectively. Oral 5-FU followed by eribulin had a numerically longer OS1 (2.84 years) than the other sequences.
Results date posted	2022 Year 05 Month 03 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	Taxane and oral 5-FU were used for 60 (33%) and 57 (32%) patients as frst-line chemotherapy, respectively. For 46 (26%) patients, eribulin was used as frst-line chemotherapy but represented second-line chemotherapy for 70 (48%) patients. The frequent frst- and secondline chemotherapy sequences were as follows: taxane followed by eribulin (n=33), oral 5-FU-based therapy followed by eribulin (n=26), eribulin followed by taxane (n=21), taxane followed by oral 5-FU (n=11), and eribulin followed by oral 5-FU (n=10). Anthracyclines or taxanes were used for 106 patients (58.9%) in the frst- or second-line chemotherapy, whereas neither anthracyclines nor taxanes were used for the remaining 74 patients (41.1%) in both lines.
Participant flow	Overall, 201 patients were enrolled during July 2015 2017. Of them, 21 (10.4%) were excluded from this study, 16patients did not receive first line chemotherapy, 2 withdrew consent, two did not meet the inclusion criteria, and one was registered erroneously. The full analysis set comprised 180 patients who underwent first line chemotherapy.
Adverse events	Patients treated with eribulin or oral 5-FU as frst-line chemotherapy had a signifcantly lower discontinuation rate owing to adverse events than those treated with anthracyclines or taxanes (p=0.038). Additionally, lower toxicity was the main reason eribulin was used as frst- and second-line chemotherapy for patients not previously treated with anthracycline/taxane.
Outcome measures	The primary endpoint was the frstline OS (OS1), defined as the time from the start of firstline chemotherapy to death from any cause. The secondary endpoints were the secondline OS (OS2) and thirdline OS (OS3), which were defined as the time from the start of second and thirdline chemotherapy, respectively. PFS, time to treatment failure (TTF), new metastasis-free survival (nMFS), and safety were evaluated as the secondary endpoints. Moreover, OS1 stratified by two age groups (65 and 65 years) was also evaluated as the exploratory adhoc analysis.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2015 Year 06 Month 25 Day
Date of IRB	2015 Year 06 Month 25 Day
Anticipated trial start date	2015 Year 07 Month 15 Day
Last follow-up date	2020 Year 01 Month 31 Day
Date of closure to data entry	2020 Year 03 Month 31 Day
Date trial data considered complete	2020 Year 03 Month 31 Day
Date analysis concluded	2020 Year 06 Month 30 Day

Other
Other related information	This study investigate overall survival of the first or second line chemotherapy in patients with HER2-negative hormone-resistant metastatic breast cancer in current clinical practice in Japan and explores whether the first or second line eribulin treatment can prolongs the overall survival. This study also explores factors affecting the survival.

Management information
Registered date	2015 Year 07 Month 03 Day
Last modified on	2022 Year 05 Month 03 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021016