Metastatic Colorectal CancerEVA26NCT07754513
Circulating Tumor Extracellular Vesicles for Non-Invasive Monitoring of Metastatic Colorectal Cancer
An observational study of Metastatic Colorectal Cancer, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Blood sample
- How many people
- 290 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2026to 1 Sep 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Circulating Tumor Extracellular Vesicles As Novel Non-invasive Biomarkers to Monitor Metastatic Colorectal Cancer Transcriptomic and Proteomic Evolution
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.
Read the 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).
Retrospective validation: validation of selected biomarkers in an independent mCRC cohort using droplet digital PCR (ddPCR) for EV-RNA and nano-flow cytometry for EV-PROT, combined with clinical outcome analyses and functional studies using CRC-org-derived 3D tumor models (assembloids).
Prospective validation: assessment of biomarker clinical value in an independent prospective mCRC cohort through longitudinal plasma analyses at different treatment time points, evaluating associations with treatment response, progression-free survival (PFS), and overall survival (OS).
The integration of molecular, clinical, and experimental data will support the biological characterization of EV-derived biomarkers and their potential role in tumor progression, therapeutic response, and resistance mechanisms.
The statistical analysis will be conducted to evaluate the association between EV-RNA and EV-PROT biomarkers and clinical disease outcomes. Data will be analyzed using descriptive methods and appropriate statistical tests to compare groups and assess changes over time.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Blood sample
- Keywords
- Circulating extracellular vesicles (EVs), Biomarker discovery
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood sampleOther
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years
Secondary outcomes (3)
Identification of EV-RNA and EV-PROT Biomarkers in Metastatic Colorectal Cancer (Discovery Phase)
The discovery phase aims to identify novel EV-RNA and EV-PROT biomarkers derived from circulating extracellular vesicles in patients with metastatic colorectal cancer (mCRC). Biomarker candidates identified in plasma samples will be integrated with spatial transcriptomic and proteomic analyses of primary tumor tissues to assess their biological relevance. Functional validation will be performed using patient-derived colorectal cancer organoids (CRC-org), evaluating the effects of chemotherapy and targeted therapies on EV-derived biomarker expression.
Measured: 3 years
Retrospective Validation of Biomarker Candidates in an Independent Cohort and Experimental Models
The identified EV-RNA and EV-PROT biomarkers will be retrospectively validated in an independent cohort of patients with metastatic colorectal cancer (mCRC). EV-RNA biomarkers will be assessed by droplet digital PCR (ddPCR), while EV-PROT biomarkers will be validated through nano-flow cytometry. Biomarker data will be integrated with clinical and pathological parameters to evaluate their association with treatment response, disease progression, and survival outcomes. Functional validation will be performed using patient-derived colorectal cancer stem cell models (CRC-org).
Measured: 3 years
Prospective Validation and Assessment of the Clinical Utility of Biomarkers
The final phase will prospectively validate EV-RNA and EV-PROT biomarkers in an independent cohort of patients with metastatic colorectal cancer (mCRC) enrolled at two participating centers. Longitudinal plasma sample analyses collected at baseline, first radiological evaluation, and disease progression will assess the association between biomarker levels and clinical outcomes, including treatment response, progression-free survival (PFS), and overall survival (OS). Data from CRC-org models and 3D assembloids will be integrated with clinical and molecular findings to support the biological interpretation of the identified biomarkers and their potential role in therapeutic response and resistance mechanisms.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2026
- Study start1 Sep 2026 (estimated)
- Primary completion1 Sep 2029 (estimated)
- Study completion1 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 290 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Donatella Lucchetti, PhD, Study director, Catholic University of the Sacred Heart
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07754513
- Sponsor's protocol ID
- 27620
- Acronym
- EVA26
- Status last verified
- Aug 2026
- First submitted
- 4 Aug 2026
- Last updated
- 10 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Circulating Tumor Extracellular Vesicles As Novel Non-invasive Biomarkers to Monitor Metastatic Colorectal Cancer Transcriptomic and Proteomic Evolution
- ClinicalTrials.gov ID
- NCT07754513
- Acronym / sponsor ID
- EVA26 / 27620
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- Circulating extracellular vesicles (EVs), Biomarker discovery
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 290 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 1 Sep 2029 (estimated)
- Study completion
- 1 Sep 2029 (estimated)
- First posted
- 10 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Retrospective validation: validation of selected biomarkers in an independent mCRC cohort using droplet digital PCR (ddPCR) for EV-RNA and nano-flow cytometry for EV-PROT, combined with clinical outcome analyses and functional studies using CRC-org-derived 3D tumor models (assembloids).
Prospective validation: assessment of biomarker clinical value in an independent prospective mCRC cohort through longitudinal plasma analyses at different treatment time points, evaluating associations with treatment response, progression-free survival (PFS), and overall survival (OS).
The integration of molecular, clinical, and experimental data will support the biological characterization of EV-derived biomarkers and their potential role in tumor progression, therapeutic response, and resistance mechanisms.
The statistical analysis will be conducted to evaluate the association between EV-RNA and EV-PROT biomarkers and clinical disease outcomes. Data will be analyzed using descriptive methods and appropriate statistical tests to compare groups and assess changes over time.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 | – | Other: Blood sampleThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood sampleCollection, 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). | Other | Prospective cohort |
Primary outcome
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.
3 secondary outcomes
Identification of EV-RNA and EV-PROT Biomarkers in Metastatic Colorectal Cancer (Discovery Phase)
Time frame: 3 years
Retrospective Validation of Biomarker Candidates in an Independent Cohort and Experimental Models
Time frame: 3 years
Prospective Validation and Assessment of the Clinical Utility of Biomarkers
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2026.
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CRC
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Donatella Lucchetti, PhD study director
Catholic University of the Sacred Heart
Questions about this trial
What is this clinical trial studying?
An observational study of Metastatic Colorectal Cancer, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Maria Alessandra Calegari, MD (0630156318, mariaalessandra.calegari@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification and Validation of Extracellular Vesicle-Derived Biomarkers in Metastatic Colorectal Cancer (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2026.