Tokyo, Oct. 1 -- UMIN Clinical Trials Registry (UMIN-CTR) received information related to the study (UMIN000062496) titled 'Sensitivity of Soft Tissue Sarcomas to KIF18A and CENP-E Inhibitors and Identification of Predictive Biomarkers' on Oct. 1.

Study Type: Observational

Primary Sponsor: Institute - Tohoku University

Condition: Condition - Soft tissue sarcoma Classification by malignancy - Malignancy Genomic information - NO

Objective: 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

Eligibility: 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 Size - 60

Recruitment Status: Recruitment status - Preinitiation Date of protocol fixation - 2026 Year 09 Month 01 Day Anticipated trial start date - 2026 Year 09 Month 21 Day Last follow-up date - 2030 Year 03 Month 31 Day

To know more, visit https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000071520

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