UMIN-ICDS Clinical Trial

Public title

Sensitivity of Soft Tissue Sarcomas to KIF18A and CENP-E Inhibitors and Identification of Predictive Biomarkers

Acronym

Drug Therapy for Chromosomal Instability in Soft Tissue Sarcomas

Scientific Title

Sensitivity of Soft Tissue Sarcomas to KIF18A and CENP-E Inhibitors and Identification of Predictive Biomarkers

Scientific Title:Acronym

Drug Therapy for Chromosomal Instability in Soft Tissue Sarcomas

Region

Japan

Condition

Soft tissue sarcoma

Classification by specialty

Hematology and clinical oncology	Surgery in general	Gastrointestinal surgery
Orthopedics

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

The purpose of this study is to evaluate the efficacy of KIF18A and CENP-E inhibitors targeting chromosomal instability (CIN) using surgical specimens from adult patients with soft tissue sarcoma and to identify biomarkers predictive of drug sensitivity. Adult patients with soft tissue sarcoma who undergo surgery or biopsy at Kameda General Hospital and provide written informed consent will be enrolled, with leiomyosarcoma as the primary focus because of its frequent copy number abnormalities and chromosomal rearrangements.
Surplus tumor tissues, newly consented research specimens, FFPE sections, and clinical information (age, sex, diagnosis, histological subtype, stage, treatment history, recurrence/metastasis, and clinical course) will be collected. Primary cell cultures and ex vivo tumor fragment cultures will be established and treated with the KIF18A inhibitor AMG650 and the CENP-E inhibitor GSK923295. Drug sensitivity will be assessed by proliferation inhibition, apoptosis/cell death, and chromosomal misalignment. Drug-sensitive tumors may be further evaluated in mouse xenograft models.
The primary endpoints are sensitivity to AMG650 and GSK923295 in primary cultured cells, including growth inhibition, IC50, caspase-3/7 activation, cell death, and chromosomal misalignment. Secondary endpoints include KIF18A and CENP-E expression, CIN status, RNA-seq and spatial transcriptomics profiles, and their association with histological subtype, clinical characteristics, and drug response. Exploratory analyses will evaluate antioxidant metabolites, secreted proteins, antioxidant response genes, and secretory factors associated with CIN using culture supernatants and transcriptomic data. These analyses aim to identify biomarkers predictive of response to KIF18A/CENP-E inhibitors, characterize responsive soft tissue sarcomas, and establish preclinical proof of concept for future patient stratification and clinical trials.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Not applicable

Primary outcomes

Drug sensitivity to AMG650 and GSK923295 in primary cultured cells derived from clinical specimens or tumor biopsies of soft tissue sarcomas

Key secondary outcomes

* Immunohistochemistry scores for KIF18A and CENP-E in tumor tissue
* RNA expression levels of KIF18A and CENP-E
* Degree of chromosomal instability
* Gene expression profiles obtained via RNA-seq
* Intratumoral heterogeneity indices obtained via spatial transcriptomics analysis
* Soft tissue sarcoma subtypes
* Clinical information, including stage, treatment history, presence or absence of recurrence or metastasis, and site of biopsy
* Clinical course, including recurrence, progression, and survival status
* Measurements of antioxidant metabolites and secreted proteins in culture supernatants
* Expression levels of genes related to the antioxidant response, redox regulation, and secreted factors
* Associations between these factors and indicators of chromosomal instability, drug sensitivity, and mitotic abnormalities

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

18

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

(1) Patients diagnosed with soft tissue sarcoma based on histological or cytological examination. Eligible histological types include leiomyosarcoma, liposarcoma, undifferentiated pleomorphic sarcoma, synovial sarcoma, and other adult soft tissue sarcomas.
(2) Patients from whom tumor tissue is collected at the study site or a collaborating institution through surgery, needle biopsy, excisional biopsy, or other clinical procedures based on clinical necessity; or patients whose soft tissue sarcoma tissue samples and clinical information, previously collected and stored for clinical purposes, can be used in this study.
(3) Patients with either a primary tumor, a locally recurrent tumor, or a metastatic lesion. While there are no restrictions on disease stage, this study targets cases from which tumor tissue necessary for drug sensitivity assessment and biomarker identification can be obtained.
(4) Patients who are 18 years of age or older at the time of enrollment. As this is a study focusing on adult soft tissue sarcomas, minors are not eligible for participation.
(5) Gender is not a factor.
(6) Patients for whom the clinical information, pathological information, treatment history, prognostic information, and other data required for this study can be obtained from medical records or other sources.
(7) Patients from whom written informed consent to participate in the study has been obtained if new samples are to be collected.
(8) Patients for whom existing specimens and information may be used in this study following information disclosure or appropriate consent procedures in accordance with ethical guidelines.
(9) Patients for whom the principal investigator or a co-investigator determines that the collected or stored tumor tissue is of sufficient quantity and quality to be used for any of the following: immunohistochemical staining, RNA-seq, spatial transcriptomics analysis, primary cell culture, drug sensitivity testing, or chromosomal instability assessment.

Key exclusion criteria

(1) Individuals determined by pathological diagnosis, medical records, or other clinical findings to have a disease other than soft tissue sarcoma.
(2) Individuals whose collected or preserved tumor tissue is insufficient in quantity or quality for the planned analyses, including primary culture, drug sensitivity testing, immunohistochemistry, RNA-seq, spatial transcriptomics, and chromosomal instability assessment.
(3) Individuals whose specimens show severe necrosis, degeneration, infection, poor fixation, or low tumor cell content that, in the judgment of the principal investigator or co-investigator, would compromise the reliability of the analyses.
(4) Individuals with concurrent or prior malignancies, multiple cancers, or severe inflammation/infection that, in the judgment of the principal investigator or co-investigator, would significantly affect drug sensitivity, gene expression, immunohistochemistry, or chromosomal instability analyses.
(5) Individuals from whom written informed consent cannot be obtained for newly collected samples, or who withdraw consent.
(6) Individuals for whom the use of existing samples or clinical information is not permitted under applicable consent or disclosure procedures, or who refuse such use.
(7) Individuals who are pregnant, possibly pregnant, breastfeeding, or planning pregnancy during the study period. This criterion may be waived when only surplus or existing specimens and information are used without additional invasive procedures or study-related treatment, if considered ethically and medically appropriate by the investigators.
(8) Individuals participating in another clinical study that may influence specimen collection, clinical data collection, drug sensitivity testing, or biomarker analyses.
(9) Any other individuals considered unsuitable for study participation or specimen/information use by the principal investigator or co-investigator.

Target sample size

60

Name of lead principal investigator

1st name	Kozo
Middle name
Last name	Tanaka

Organization

Institute of Development, Aging and Cancer, Tohoku University

Division name

Department of Molecular Oncology

Zip code

980-8575

Address

4-1 Seiryo-machi, Aoba-ku, Sendai

TEL

022-717-8491

Email

kozo.tanaka.d2@tohoku.ac.jp

Name of contact person

1st name	Yukiko
Middle name
Last name	Mita

Organization

Institute of Development, Aging and Cancer, Tohoku University

Division name

Department of Molecular Oncology

Zip code

980-8575

Address

4-1 Seiryo-machi, Aoba-ku, Sendai

TEL

022-717-8490

Homepage URL

Email

yukiko.mita.e5@tohoku.ac.jp

Institute

Tohoku University

Institute

Department

Personal name

Organization

Tohoku University

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Ethics Committee of the Graduate School of Medicine, Tohoku University

Address

2-1 Seiryo-machi, Aoba-ku, Sendai

Tel

022-728-4105

Email

ec-med@grp.tohoku.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

Date of disclosure of the study information

2026

Year

10

Month

01

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

2026

Year

09

Month

01

Day

Date of IRB

Anticipated trial start date

2026

Year

09

Month

21

Day

Last follow-up date

2030

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

This is a multicenter, prospective observational study designed to evaluate the sensitivity of soft tissue sarcomas to KIF18A and CENP-E inhibitors and to identify predictive biomarkers using tumor specimens, FFPE sections, and clinical information obtained from adult patients undergoing clinically indicated surgery or biopsy at Kameda General Hospital. No therapeutic intervention, study-related drug administration, treatment modification, or additional invasive procedures will be performed. Only surplus specimens obtained during routine clinical care or specimens collected with informed consent for research will be used.
Clinical information, including age, sex, histological subtype, disease stage, treatment history, recurrence or metastasis, and clinical course, will be collected. Primary cell cultures will be established from tumor tissues, and short-term ex vivo drug sensitivity assays will be performed using tumor fragments. Sensitivity to the KIF18A inhibitor AMG650 and the CENP-E inhibitor GSK923295 will be evaluated by measuring cell proliferation inhibition, IC50, caspase-3/7 activation, cell death, and chromosome misalignment. Immunohistochemical analysis of KIF18A and CENP-E expression, assessment of chromosomal instability (CIN), RNA sequencing, and spatial transcriptomics will be performed to examine their association with drug sensitivity. Exploratory analyses in selected specimens will evaluate antioxidant metabolites and secreted proteins in culture supernatants and reanalyze RNA-seq and spatial transcriptomics data for CIN-related, antioxidant response, and secretory factor-related genes associated with drug sensitivity. When appropriate, drug-sensitive patient-derived cells will be further evaluated in mouse xenograft models. These analyses aim to identify soft tissue sarcomas responsive to KIF18A and CENP-E inhibitors and establish predictive biomarkers for future patient stratification and clinical trials.

Registered date

2026

Year

08

Month

06

Day

Last modified on

2026

Year

08

Month

06

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000071520