Diagnostic and Therapeutic Targets in Cartilaginous Tumours

NCT07315542 | Recruiting

• 1 other identifier: NW25-10-00260
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

This study, "Finding new diagnostic and therapeutic targets in cartilaginous tumours," focuses on improving the diagnosis, prognostic stratification, and treatment options for chondroid tumours, particularly chondrosarcoma. Chondrosarcoma is the most common primary malignant bone tumour in adults and is characterized by resistance to chemotherapy and radiotherapy, making accurate diagnosis and optimal surgical management critical. Distinguishing benign cartilage tumours (enchondromas, atypical cartilaginous tumours) from low-grade chondrosarcoma, and differentiating chondrosarcoma from chondroblastic osteosarcoma, remain major diagnostic challenges. The project investigates two key molecular markers: mutations in IDH1/2 genes and non-coding microRNAs (miRNAs). IDH1/2 mutations are frequent in central chondrosarcomas and rare in other mesenchymal tumours, making them promising diagnostic markers. Their presence may also have prognostic significance and therapeutic relevance, as IDH inhibitors are already available for other malignancies. In parallel, deregulated miRNA expression has been implicated in chondrosarcoma biology, influencing tumour growth, invasion, angiogenesis, metastasis, and chemosensitivity. Preliminary data identified distinct miRNA signatures in chondrosarcoma compared with healthy cartilage, including previously unreported miRNAs. The study is structured into exploratory and validation phases. Global miRNA expression profiling and IDH1/2 mutation analysis will be performed using next-generation sequencing (NGS) on prospectively collected fresh-frozen tumour samples. Selected miRNAs and IDH1/2 mutation status will then be validated by RT-qPCR and targeted mutation assays in a large retrospective cohort of FFPE samples. Molecular data will be integrated with clinicopathological parameters to develop diagnostic panels capable of accurately classifying chondroid tumours, as well as prognostic miRNA panels associated with patient survival. Additionally, the project evaluates circulating and exosomal miRNAs in liquid biopsies, aiming to establish non-invasive diagnostic and prognostic tools. Functional relevance will be explored using chondrosarcoma cell lines with simulated miRNA upregulation, coupled with transcriptomic analysis. Overall, the study seeks to refine diagnostic accuracy, improve prognostic assessment, and identify novel molecular targets for personalized and targeted therapy in patients with inoperable or metastatic chondrosarcoma, addressing a major unmet clinical need.

Conditions

Chondrosarcomas; Cartilage Tumours

Keywords

Chondrosarcoma; Liquid biopsy; Targeted therapy; Prognostic markers; Molecular biomarkers; MicroRNA (miRNA); Cartilaginous tumours; IDH1 mutation; IDH2 mutation

Outcome Measures

Primary Outcomes (2)

• Diagnostic accuracy of molecular markers

  Ability of IDH1/2 mutation status and tumour tissue miRNA expression profiles to: Distinguish benign cartilaginous tumours (enchondromas, atypical cartilaginous tumours) from malignant tumours (chondrosarcomas). Distinguish chondrosarcoma from chondroblastic osteosarcoma. Outcomes will be quantified using molecular classification performance (e.g. correct stratification against histopathological diagnosis) based on NGS and RT-qPCR analyses.

  From May 2025 to December 2027

• Identification of prognostic molecular signatures

  Association between IDH1/2 mutation status and overall survival of patients with malignant cartilaginous tumours. Identification of prognostic miRNA panels whose expression profiles stratify patients into different survival risk groups.

  From May 2025 to December 2027

Secondary Outcomes (2)

• Validation of candidate biomarkers

  From May 2025 to December 2027

• Liquid biopsy feasibility

  From May 2025 to December 2027

Study Arms (1)

Patients with cartilaginous bone tumours

The study cohort consists of patients with cartilaginous bone tumours treated at a tertiary orthopaedic oncology centre. This includes individuals with benign, borderline, and malignant chondroid lesions across the full biological spectrum, namely enchondromas, atypical cartilaginous tumours (ACT/G1), conventional chondrosarcomas (grades G1-G3), dedifferentiated chondrosarcomas, and selected rare variants. Interventions of interest in this study are primarily diagnostic and molecular, rather than therapeutic in the interventional trial sense. Molecular analysis of tumour tissue using next-generation sequencing (NGS) to assess global microRNA expression profiles and IDH1/2 mutation status. Validation of selected molecular markers using RT-qPCR and targeted mutation detection assays. Analysis of circulating and exosomal microRNAs from blood as a form of liquid biopsy. Experimental miRNA modulation to investigate biological relevance in relation to IDH1/2 mutation status.

Diagnostic Test: Tumour tissue analysis; Diagnostic Test: Molecular validation; Diagnostic Test: Liquid biopsy analysis

Interventions

Molecular validation DIAGNOSTIC_TEST

Quantitative reverse transcription PCR (RT-qPCR) to validate selected miRNAs Targeted molecular assays for confirmation of IDH1/2 mutations

Patients with cartilaginous bone tumours

Liquid biopsy analysis DIAGNOSTIC_TEST

Assessment of circulating and exosomal miRNAs from patient body fluids as non-invasive biomarkers

Patients with cartilaginous bone tumours

Tumour tissue analysis DIAGNOSTIC_TEST

Next-generation sequencing (NGS) to determine IDH1/2 mutation status Global microRNA (miRNA) expression profiling using NGS

Patients with cartilaginous bone tumours

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of patients with cartilaginous (chondroid) tumours treated at the First Department of Orthopaedic Surgery, St. Anne's University Hospital Brno, a national referral centre for bone tumours.

You may qualify if:

• Histologically confirmed cartilaginous (chondroid) tumour
• Diagnosis includes one of the following entities (as available and eligible):
• Enchondroma
• Atypical cartilaginous tumour / Grade 1 chondrosarcoma (ACT/G1)
• Conventional chondrosarcoma (Grade 2-3)
• Dedifferentiated chondrosarcoma
• Other rare chondrosarcoma variants (e.g., mesenchymal, clear-cell), if present in the cohort
• Patients treated and/or followed at the First Department of Orthopaedic Surgery, St. Anne's University Hospital Brno

You may not qualify if:

• Insufficient, degraded, or otherwise unusable tissue samples

Sponsors & Collaborators

• St. Anne's University Hospital Brno, Czech Republic: lead
• Masaryk University: collaborator

Study Sites (1)

First Department of Orthopaedic Surgery, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czechia

Brno, South Moravian, 60200, Czechia

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

tumor samples blood samples

MeSH Terms

Conditions

Chondrosarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Study Officials

• Tomáš Tomáš, Assoc.Prof., M.D., Ph.D.

  Faculty of Medicine, Masaryk University, Brno, 60200, Czechia

  PRINCIPAL INVESTIGATOR

• Michal Mahdal, M.D., Ph.D.

  First Department of Orthopaedic Surgery, St. Anne's University Hospital, Brno, 60200, Czechia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vasileios Apostolopoulos, M.D., Ph.D.

CONTACT

+420722101065; vasileios.apostolopoulos@fnusa.cz

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2025
• First Posted: January 2, 2026
• Study Start: May 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 5, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)