Circulating Tumor Extracellular Vesicles As Novel Non-invasive Biomarkers to Monitor Metastatic Colorectal Cancer Transcriptomic and Proteomic Evolution
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Enrollment
- 290
- Primary Endpoint
- Identification and Validation of Extracellular Vesicle-Derived Biomarkers in Metastatic Colorectal Cancer
Study Overview
Brief Summary
Metastatic colorectal cancer (mCRC) remains a major clinical challenge due to heterogeneous treatment responses and the development of therapeutic resistance. Current tissue-based molecular profiling is limited by invasiveness and the inability to enable longitudinal monitoring. Extracellular vesicles (EVs) represent a promising source of non-invasive biomarkers, carrying stable RNA and proteins reflective of tumor biology. This study aims to identify and validate EV-derived transcriptomic and proteomic biomarkers to monitor disease evolution, predict treatment response, and support personalized management of patients with mCRC.
Detailed Description
Observational, ambispective, multicenter, non-interventional study without drugs or medical devices, aimed at the identification, validation, and clinical evaluation of extracellular vesicle (EV)-derived biomarkers in patients with metastatic colorectal cancer (mCRC).
The study will include patients diagnosed with metastatic colorectal cancer (mCRC), divided into a retrospective cohort and a prospective cohort.
This study aims to identify and validate circulating extracellular vesicle (EV)-derived biomarkers, including EV-RNA and EV-protein (EV-PROT) profiles, in patients with metastatic colorectal cancer (mCRC). The goal is to develop an integrated non-invasive biomarker panel to support patient stratification, treatment response prediction, and longitudinal disease monitoring.
The study will be conducted through three main phases:
Discovery phase: identification of novel EV-RNA and EV-PROT biomarkers from plasma samples of mCRC patients, integrated with spatial transcriptomic and proteomic analyses of tumor tissues and functional evaluation in patient-derived colorectal cancer organoids (CRC-org).
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Other
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Retrospective Cohort Inclusion Criteria:
- •Age ≥ 18 years;
- •Histologically confirmed diagnosis of colorectal adenocarcinoma;
- •Radiological evidence of metastatic or locally advanced unresectable disease;
- •First-line treatment for metastatic disease already completed or ongoing according to standard clinical practice;
- •Availability of stored biological samples collected at least at one of the protocol-defined time points (baseline, post-treatment, disease progression);
- •Informed consent acquisition will be performed in accordance with Article 110-bis of the Italian Privacy Code.
- •Retrospective Cohort
Exclusion Criteria
- •Absence of suitable biological samples or samples unsuitable for molecular analyses;
- •Incomplete clinical data preventing the performance of the planned analyses;
- •Insufficient quality of stored biological samples for the assessment of EV-RNA and EV-PROT analyses.
- •Prospective Cohort Inclusion Criteria:
- •Age ≥ 18 years;
- •Histologically confirmed diagnosis of colorectal adenocarcinoma;
- •Radiological evidence of unresectable metastatic disease;
- •Patients not previously treated for metastatic disease (prior completed adjuvant/neoadjuvant therapy is allowed if completed ≥ 6 months before study enrollment);
- •Indication for first-line treatment with chemotherapy ± biological therapy according to standard clinical practice;
- •Ability to understand the study procedures and provide written informed consent.
- •Prospective Cohort Exclusion Criteria:
- •Previous systemic treatment for metastatic disease (except prior adjuvant/neoadjuvant therapy as specified above);
- •Ongoing pregnancy or breastfeeding;
- •Legal incapacity or limitation in the ability to provide informed consent.
Arms & Interventions
Retrospective cohort
The retrospective cohort will include 160 patients with metastatic colorectal cancer (mCRC) who have previously received first-line systemic therapy (chemotherapy with or without targeted biological agents). Biological samples and corresponding clinical data, collected as part of routine clinical practice between 2017 and 2025, will be retrospectively analyzed.
Prospective cohort
The prospective cohort will include 130 treatment-naïve patients with metastatic colorectal cancer (mCRC) who will be prospectively enrolled at the start of first-line systemic therapy for longitudinal collection of biological samples and clinical data.
Intervention: Blood sample (Other)
Outcomes
Primary Outcomes
Identification and Validation of Extracellular Vesicle-Derived Biomarkers in Metastatic Colorectal Cancer
Time Frame: 3 years
The study aims to identify and validate circulating extracellular vesicle (EV)-derived biomarkers, including EV-RNA and EV-protein (EV-PROT) signatures, in patients with metastatic colorectal cancer (mCRC). The objective is to develop and validate an integrated, non-invasive biomarker panel to support patient stratification, predict response to systemic therapies, and enable longitudinal monitoring of disease evolution throughout treatment.
Secondary Outcomes
- Identification of EV-RNA and EV-PROT Biomarkers in Metastatic Colorectal Cancer (Discovery Phase)(3 years)
- Retrospective Validation of Biomarker Candidates in an Independent Cohort and Experimental Models(3 years)
- Prospective Validation and Assessment of the Clinical Utility of Biomarkers(3 years)