Renal Cell Carcinoma
Conditions
Keywords
Extracellular vesicles, Liquid biopsy
Brief summary
This study investigates the role of circulating and urinary exosomal microRNAs (miRNAs) as potential biomarkers for predicting response to systemic therapy in patients with advanced renal cell carcinoma. Patients receiving immune checkpoint inhibitors or targeted therapies are followed during the first 16 weeks of treatment. Blood and urine samples are collected at predefined time points for analysis of exosome-associated miRNAs. Imaging assessments are performed as part of routine clinical follow-up. The aim of the study is to identify exosomal miRNA profiles associated with treatment response and to support the development of non-invasive predictive biomarkers in advanced kidney cancer.
Detailed description
Advanced renal cell carcinoma is commonly treated with immune checkpoint inhibitors and targeted therapies; however, patient response is heterogeneous and reliable predictive biomarkers are limited. Exosomes are extracellular vesicles released by cells into body fluids and contain molecular cargo such as microRNAs (miRNAs), which may reflect tumor biology and immune response. Circulating and urinary exosomal miRNAs represent promising non-invasive biomarkers that could support early prediction of treatment response. This prospective clinical study evaluates changes in the expression of selected exosome-associated miRNAs in blood and urine and their association with response to systemic therapy in patients with advanced renal cell carcinoma. Eligible participants include patients treated in the first- or second-line setting with immune checkpoint inhibitors or targeted agents. Participants provide blood samples (approximately 10 mL) at four predefined time points and urine samples (approximately 50 mL) at two predefined time points during the first 16 weeks of therapy. Samples are processed according to a standardized protocol including centrifugation and storage at low temperature until further analysis. Laboratory procedures include isolation of extracellular vesicles from plasma and urine, quantification of extracellular vesicles using nanoparticle tracking analysis, and isolation of exosome-associated miRNA followed by quantitative PCR (qPCR) for selected target miRNAs. Quality assessment of samples is performed, including evaluation of hemolysis and additional purity controls. Clinical data and radiological imaging results collected during routine clinical management are used to assess treatment response. The primary objective is to identify associations between exosomal miRNA expression patterns and treatment response during early therapy. The study aims to contribute to the development of minimally invasive biomarkers for prediction of therapy response in advanced kidney cancer and to improve patient stratification for systemic treatment.
Interventions
DIAGNOSTIC_TESTCirculating and Urinary Exosomal miRNA Analysis
Blood and urine samples are collected at predefined time points during the first 16 weeks of systemic therapy. Exosomes (extracellular vesicles) are isolated from plasma and urine, quantified, and exosome-associated microRNAs are extracted and analyzed using quantitative PCR (qPCR). The intervention is performed to evaluate exosomal miRNA profiles as predictive biomarkers of treatment response in advanced renal cell carcinoma.
Sponsors
Institute of Oncology Ljubljana
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults (≥18 years) * Histologically confirmed advanced or metastatic renal cell carcinoma * Receiving systemic treatment with immune checkpoint inhibitors and/or targeted therapy (first- or second-line therapy) * Ability to provide blood and urine samples according to the study protocol * Written informed consent
Exclusion criteria
* Age \<18 years * Inability to provide required blood and urine samples * Inability to provide informed consent * Any condition preventing participation according to investigator assessment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Circulating Exosomal miRNA Relative Expression (ΔCt) Measured by Quantitative PCR | Baseline to Week 16 | Change from baseline to Week 16 in selected circulating exosome-associated microRNA expression levels measured in plasma using quantitative polymerase chain reaction (qPCR). Expression is quantified as relative cycle threshold values (ΔCt). |
| Radiological Response Rate Assessed by RECIST 1.1 | Week 16 | Radiological treatment response at Week 16 assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Response categories include Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD). Outcome reported as proportion of patients in each response category. |
| Spearman Correlation Coefficient Between Change in Circulating Exosomal miRNA Expression (ΔCt) and Radiological Response (RECIST 1.1) | Week 16 | Spearman correlation coefficient (rho) between change from baseline to Week 16 in circulating exosomal miRNA relative expression levels (ΔCt, measured by qPCR) and radiological treatment response at Week 16 assessed using RECIST version 1.1. |
Countries
Slovenia
Outcome results
None listed