Circulating Tumor Extracellular Vesicles for Non-Invasive Monitoring of Metastatic Colorectal Cancer

NCT07754513 | Not Yet Recruiting

• 1 other identifier: 27620
• Study Type: observational
• Target: 290
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Metastatic Colorectal Cancer

Keywords

Circulating extracellular vesicles (EVs); Biomarker discovery

Outcome Measures

Primary Outcomes (1)

• Identification and Validation of Extracellular Vesicle-Derived Biomarkers in Metastatic Colorectal Cancer

  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.

  3 years

Secondary Outcomes (3)

• 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

Study Arms (2)

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.

Other: Blood sample

Interventions

Blood sample OTHER

Collection, in conjunction with blood sampling performed as part of routine clinical practice, of a 9 mL blood sample in an EDTA tube at the following time points: before treatment initiation, at the first radiological reassessment, and at disease progression. This sample collection is part of the standard clinical management of patients with metastatic colorectal cancer (mCRC).

Prospective cohort

Eligibility Criteria

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

Study Population

The retrospective cohort will include a total of 160 patients with metastatic colorectal cancer (mCRC) who have already received first-line systemic therapy (chemotherapy with or without biological agents), for whom biological samples and clinical data collected as part of routine clinical practice are available. Biological sample collection is planned for the period from 2017 to 2025. The prospective cohort will include 130 treatment-naïve patients with mCRC, who will be enrolled at the initiation of first-line therapy.

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Donatella Lucchetti, PhD

  Catholic University of the Sacred Heart

  STUDY DIRECTOR

Central Study Contacts

Maria Alessandra Calegari, MD

CONTACT

0630156318; mariaalessandra.calegari@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2026
• First Posted: August 10, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: August 10, 2026

Record last verified: 2026-08