UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000041493 |
|---|---|
| Receipt number | R000047323 |
| Scientific Title | A multi-institutional, retrospective, translational study of the relationship between histological immune-related signatures and clinical benefit of paclitaxel + bevacizumab therapy in HER2-negative advanced breast cancer |
| Date of disclosure of the study information | 2020/09/01 |
| Last modified on | 2026/05/19 09:59:54 |
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Basic information
Public title
A multi-institutional, retrospective, translational study of the relationship between histological immune-related signatures and clinical benefit of paclitaxel + bevacizumab therapy in HER2-negative advanced breast cancer
Acronym
TRI-BE study
Scientific Title
A multi-institutional, retrospective, translational study of the relationship between histological immune-related signatures and clinical benefit of paclitaxel + bevacizumab therapy in HER2-negative advanced breast cancer
Scientific Title:Acronym
TRI-BE study
Region
| Japan |
Condition
Condition
HER2-negative advanced breast cancer
Classification by specialty
| Hematology and clinical oncology |
Classification by malignancy
Malignancy
Genomic information
NO
Objectives
Narrative objectives1
To explore pathological biomarkers for PB therapy by retrospective evaluation of the association between immune-related signatures of archived tissue and clinical efficacy of PB therapy.
Basic objectives2
Others
Basic objectives -Others
Exploring pathological biomarkers for PB therapy.
Trial characteristics_1
Exploratory
Trial characteristics_2
Developmental phase
Not applicable
Assessment
Primary outcomes
1.Expression-status of immune-related signatures in primary site
2.Relationships between overall survival (OS)/time-to-treatment failure (TTF) and expression status of immune-related signatures in primary site
Key secondary outcomes
1.Relationships between overall survival (OS)/time-to-treatment failure (TTF) and expression-status of immune-related signatures in metastatic site
2.Relationships between peripheral immune-related markers/nutritional markers and expression-status of immune-related signatures in metastatic site
3.Changes in markers of epithelial-mesenchymal transition between primary site and metastatic site
4.Relationships between peripheral immune-related markers/nutritional markers and clinical efficacy
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
| Not applicable |
Age-upper limit
| Not applicable |
Gender
Male and Female
Key inclusion criteria
HER2-ABC patients who underwent PB therapy as their first-/second- line chemotherapy between January 2011 to December 2016 at participating institutes (Shizuoka Cancer Center, Hiroshima City Hiroshima Citizens Hospital, and Fukuyama City Hospital)
Key exclusion criteria
Not applicable
Target sample size
156
Research contact person
Name of lead principal investigator
| 1st name | Takashi |
| Middle name | |
| Last name | Sugino |
Organization
Shizuoka Cancer Center, Shizuoka
Division name
Division of Pathology
Zip code
411-8777
Address
1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka
TEL
055-989-5222
t.sugino@scchr.jp
Public contact
Name of contact person
| 1st name | Junichiro |
| Middle name | |
| Last name | Watanabe |
Organization
Shizuoka Cancer Center, Shizuoka
Division name
Division of Breast Oncology
Zip code
411-8777
Address
1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka
TEL
055-989-5222
Homepage URL
j.watanabe@scchr.jp
Sponsor or person
Institute
The Mt.Fuji Foundation for Healthcare Innovation and Cluster Development Pharma Valley Center
Institute
Department
Personal name
Funding Source
Organization
Chugai Pharmaceutical Co., Ltd.
Organization
Division
Category of Funding Organization
Profit organization
Nationality of Funding Organization
Japan
Other related organizations
Co-sponsor
Biomedical Statistics and Bioinformatics, Kyoto University
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Shizuoka Cancer Center Institutional Review Board
Address
1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka
Tel
055-989-5222
tansaku_office@scchr.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
静岡県立静岡がんセンター（静岡県）、広島市立広島市民病院（広島県）、福山市立福山市民病院（広島県）
Shizuoka Cancer Center (Shizuoka prefecture), Hiroshima City Hiroshima Citizens Hospital (Hiroshima pref.), Fukuyama City Hospital (idem)
Other administrative information
Date of disclosure of the study information
| 2020 | Year | 09 | Month | 01 | Day |
Related information
URL releasing protocol
Not Applicable
Publication of results
Unpublished
Result
URL related to results and publications
Due to changes in treatment and pathology, publication was not pursued.
Number of participants that the trial has enrolled
112
Results
The results of this study demonstrated that: (1) the PD-L1 expression rate in HER2-negative advanced or recurrent breast cancer was lower than previously reported; (2) PD-L1 positivity was neither a prognostic nor a predictive factor for treatment efficacy in patients receiving PB therapy; and (3) in PB therapy as a first-line treatment, the peripheral blood neutrophil-to-lymphocyte ratio at the start of the second cycle may serve as a predictive marker of treatment efficacy.
Results date posted
| 2026 | Year | 05 | Month | 19 | Day |
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Of the 156 cases, 112 were evaluable. Among the unevaluable cases, excluding two HER2-positive cases, a substantial proportion were deemed unsuitable due to inadequate tumor cell content in the specimens or difficulty in obtaining samples from non-participating institutions. Most of these cases had received prior neoadjuvant chemotherapy.
The median age at diagnosis of advanced or recurrent disease among evaluable cases was 55.5 years.
Estrogen receptor status was positive in 79 cases (70.5%), negative in 22 cases (19.6%), and unknown in 11 cases (9.8%).
PB therapy was administered as first-line treatment in 85 cases (75.9%).
Peripheral blood immune-related markers were evaluable in 38 cases.
Participant flow
The study population consisted of 156 patients who initiated PB therapy as first- or second-line chemotherapy for HER2-negative advanced breast cancer (HER2-ABC) at participating institutions (Shizuoka Cancer Center, Hiroshima City Hiroshima Citizens Hospital, and Fukuyama City Hospital) between January 1, 2011, and December 31, 2016.
Pathological specimens of the primary tumor stored at the participating institutions (15 unstained slides or formalin-fixed paraffin-embedded tissue blocks) were submitted to a central pathology review institution (Department of Pathology, Shizuoka Cancer Center) for assessment of PD-L1 expression in the primary tumor. In cases where pathological specimens from both primary and metastatic lesions were available, changes in immune-related signatures and epithelial-mesenchymal transition markers were also evaluated in both sites.
These findings were statistically analyzed in relation to clinical outcomes to identify potential pathological biomarkers predictive of response to PB therapy.
Adverse events
Adverse events were not assessed in this retrospective study.
Outcome measures
Primary endpoints
(1) The overall PD-L1 positivity rate was 9 cases (8.0%).
(2) The median overall survival (OS) was 1.7 years in PD-L1 positive cases and 2.7 years in PD-L1 negative cases; however, no statistically significant difference was observed by the log-rank test (P = 0.089). The median time to treatment failure (TTF) for first-line therapy was 3.6 months and 6.8 months, respectively, with a statistically significant difference observed by the log-rank test (P = 0.003).
Secondary endpoints
(3) Due to the limited number of cases, no biologically or clinically meaningful findings were observed.
(4) Peripheral blood immune-related markers were evaluable in 38 cases. No correlation was observed between these markers at the initiation of first-line PB therapy and OS or TTF; however, a low peripheral blood neutrophil to lymphocyte ratio at the start of the second cycle was considered a potential predictive factor for the efficacy of PB therapy.
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
Completed
Date of protocol fixation
| 2020 | Year | 07 | Month | 02 | Day |
Date of IRB
| 2020 | Year | 08 | Month | 21 | Day |
Anticipated trial start date
| 2020 | Year | 09 | Month | 09 | Day |
Last follow-up date
| 2021 | Year | 02 | Month | 08 | Day |
Date of closure to data entry
Date trial data considered complete
Date analysis concluded
Other
Other related information
Relationships between peripheral immune-related markers and efficacy of anticancer therapy have been reported, however, relationship between peripheral immune-related markers and local immune-related signatures has not been clarified yet. To clarify this unsolved clinical question, this retrospective, translational study was planned.
Management information
Registered date
| 2020 | Year | 08 | Month | 21 | Day |
Last modified on
| 2026 | Year | 05 | Month | 19 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047323
