UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000058603 |
|---|---|
| Receipt number | R000067008 |
| Scientific Title | Association Between Alpha-2-glycoprotein 1 (ZAG) Expression and Therapeutic Response in Triple-negative Breast Cancer Patients Treated with Immune Checkpoint Inhibitors |
| Date of disclosure of the study information | 2025/07/25 |
| Last modified on | 2025/07/28 11:52:57 |
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Basic information
Public title
A Study on the Association Between Alpha-2-glycoprotein 1, zinc-binding and Immune Checkpoint Inhibitor Resistance in Breast Cancer
Acronym
ZAG-ICI Resistance in Breast Cancer
Scientific Title
Association Between Alpha-2-glycoprotein 1 (ZAG) Expression and Therapeutic Response in Triple-negative Breast Cancer Patients Treated with Immune Checkpoint Inhibitors
Scientific Title:Acronym
ZAG Expression and ICI Response in TNBC
Region
| Japan |
Condition
Condition
Breast Cancer
Classification by specialty
| Breast surgery |
Classification by malignancy
Malignancy
Genomic information
NO
Objectives
Narrative objectives1
This study investigates the association between the expression of Alpha-2-glycoprotein 1 (ZAG) and therapeutic response in triple-negative breast cancer (TNBC) patients treated with immune checkpoint inhibitor (ICI)-based neoadjuvant chemotherapy (NAC). ZAG, secreted in an androgen receptor-dependent manner, has been reported to contribute to the formation of an immunosuppressive tumor microenvironment (TME), which may underlie ICI resistance. By retrospectively analyzing pre-treatment biopsy samples, we aim to clarify whether ZAG contributes to ICI resistance through immunosuppressive TME and to evaluate its potential as a predictive biomarker and therapeutic target.
Basic objectives2
Others
Basic objectives -Others
To explore ZAG's role as an immune-regulatory factor, we will analyze its association with established immune markers, including tumor infiltrating lymphocytes (TILs), PDL1 expression, HLA class I, and CD8 T-cell localization. This aims to clarify ZAG's immunomodulatory function and its relevance to ICI sensitivity.
Trial characteristics_1
Confirmatory
Trial characteristics_2
Explanatory
Developmental phase
Not applicable
Assessment
Primary outcomes
To evaluate the association between pre-treatment ZAG expression level (measured by H-score in IHC) and pathological complete response (pCR; ypT0/isN0 or ypT0N0) in triple-negative breast cancer (TNBC) patients treated with ICI-based neoadjuvant chemotherapy (Keynote-522 regimen).
Key secondary outcomes
Association between ZAG expression and tumor-infiltrating lymphocyte (TIL) density
Association between ZAG expression and PD-L1 expression (combined positive score using 22C3 antibody)
Association between ZAG expression and HLA class I expression (H-score using EMR8-5 antibody)
Association between ZAG expression and CD8+ T-cell localization patterns (Inflamed / Excluded / Desert)
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
| Not applicable |
Gender
Male and Female
Key inclusion criteria
Histologically confirmed triple-negative breast cancer (TNBC), clinical stage II or III
Received neoadjuvant chemotherapy including the immune checkpoint inhibitor according to the Keynote-522 regimen: four cycles of paclitaxel plus carboplatin plus pembrolizumab, followed by four cycles of epirubicin plus cyclophosphamide plus pembrolizumab
Availability of pre-treatment core needle biopsy specimen preserved as FFPE tissue
Underwent curative-intent breast surgery, with pathological evaluation of treatment response (pCR) feasible
Informed consent obtained for retrospective research, or eligible under opt-out policy
Key exclusion criteria
Patients with a history or presence of malignancies other than breast cancer
Patients whose pre-treatment biopsy specimens are not properly preserved as FFPE tissue
Cases in which pathological response after surgery cannot be evaluated
Cases in which treatment was initiated outside the designated study period
Cases with incomplete clinical records or pathological information that preclude required analyses
Target sample size
110
Research contact person
Name of lead principal investigator
| 1st name | Toru |
| Middle name | |
| Last name | Hanamura |
Organization
Tokai University
Division name
Department of Breast oncology
Zip code
259-1193
Address
143 Shimokasuya, Isehara-shi, Kanagawa
TEL
0463-93-1121
hanamura.toru.w@tokai.ac.jp
Public contact
Name of contact person
| 1st name | Toru |
| Middle name | |
| Last name | Hanamura |
Organization
Tokai University
Division name
Department of Breast Oncology
Zip code
259-1193
Address
143 Shimokasuya, Isehara-shi, Kanagawa
TEL
0463-93-1121
Homepage URL
hanamura.toru.w@tokai.ac.jp
Sponsor or person
Institute
Tokai University
Institute
Department
Personal name
Toru Hanamura
Funding Source
Organization
Tokai University
Organization
Division
Category of Funding Organization
Other
Nationality of Funding Organization
Japan
Other related organizations
Co-sponsor
Department of Gastrointestinal and Surgical Oncology, Yokohama City University School of Medicine
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Tokai University
Address
Tokai University School of Medicine
Tel
0463-93-1121
tokai-rec@tokai.ac.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
神奈川県
Institutions
Institutions
Other administrative information
Date of disclosure of the study information
| 2025 | Year | 07 | Month | 25 | Day |
Related information
URL releasing protocol
NA
Publication of results
Unpublished
Result
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
Progress
Recruitment status
Preinitiation
Date of protocol fixation
| 2025 | Year | 07 | Month | 25 | Day |
Date of IRB
Anticipated trial start date
| 2025 | Year | 09 | Month | 01 | Day |
Last follow-up date
| 2032 | Year | 03 | Month | 31 | Day |
Date of closure to data entry
Date trial data considered complete
Date analysis concluded
Other
Other related information
NA
Management information
Registered date
| 2025 | Year | 07 | Month | 25 | Day |
Last modified on
| 2025 | Year | 07 | Month | 28 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000067008
