Extracellular Vesicles and Chemotherapy-Induced Peripheral Neuropathy (CHEMOVES)

April 23, 2026 updated by: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Extracellular Vesicles as Predictive Biomarkers for Chemotherapy-Induced Peripheral Neuropathy

The goal of this clinical trial is to learn whether extracellular vesicles (EVs) in the blood can be used as biomarkers to predict chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer patients receiving chemotherapy with taxanes, platinum compounds, or antimitotic drugs. The main questions the study aims to answer are whether blood levels of EVs change in patients who develop CIPN during and after chemotherapy and whether specific features of EVs, including lipids and microRNAs, are associated with the development and severity of CIPN. Participants will be followed from before the start of chemotherapy until six months after treatment ends to evaluate how changes in EVs relate to nerve damage caused by chemotherapy. During the study, participants will provide blood samples before chemotherapy, at the end of treatment, and six months later for measurement and molecular analysis of EVs, will complete questionnaires about neuropathy symptoms, and will undergo simple, non-invasive nerve function tests using a tuning fork (diapason) and a Neuropen device. This study does not test cancer drugs; instead, it aims to identify biological markers in blood that may help predict which patients are at higher risk of developing CIPN, with the goal of improving monitoring and care during cancer treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

CIPN is a frequent and often long-lasting complication of treatment with several commonly used antineoplastic agents, including taxanes, platinum compounds, and antimitotic drugs. The condition primarily affects sensory neurons of the dorsal root ganglia and peripheral nerve fibers, leading to symptoms such as numbness, tingling, pain, and loss of vibration or tactile sensation. The severity and persistence of CIPN vary markedly between individuals, and currently there are no validated biological markers that allow early identification of patients at increased risk or objective monitoring of neurotoxicity during treatment. As a result, CIPN is usually detected only after clinical symptoms appear, at a stage when nerve damage may already be established and difficult to reverse.

EVs are membrane-bound particles released by virtually all cell types and present in large numbers in biological fluids, including blood. They contain proteins, lipids, and nucleic acids that reflect the physiological and pathological state of their cells of origin. Because EVs can originate from neural and glial cells and can cross biological barriers, they provide a potential window into otherwise inaccessible tissues such as the peripheral nervous system. Changes in EV concentration, membrane composition, and RNA cargo have been reported in several neurological and neurodegenerative conditions, supporting their potential role as circulating indicators of neuronal injury and dysfunction.

This study is designed to evaluate whether longitudinal changes in circulating EVs are associated with the development of CIPN in patients undergoing chemotherapy. Blood samples collected at predefined time points will be used to isolate and quantify EVs and to characterize selected molecular components of their cargo, including membrane lipids and microRNAs. These EV-based measurements will be evaluated in relation to standardized clinical and neurophysiological assessments of peripheral neuropathy performed over the course of treatment and follow-up. By integrating biological and clinical data, the study aims to explore whether EV-derived markers reflect early neurotoxic effects of chemotherapy and whether they may capture individual susceptibility to CIPN.

The study uses a single-group, longitudinal design in which each participant serves as their own reference over time. This approach allows the evaluation of intra-individual changes in EV-related parameters across the different phases of chemotherapy exposure and recovery. It is particularly suited for biomarker discovery in conditions such as CIPN, where baseline inter-individual variability is high and where the key biological signal of interest is the change from an individual's pre-treatment state. This design also avoids the need for a concurrent untreated control group, which would not be ethically or clinically appropriate in this setting.

EVs will be isolated from plasma using standardized protocols designed to preserve vesicle integrity and minimize contamination from non-vesicular particles. Quantitative analysis will be performed to determine the concentration of circulating EVs, expressed as vesicles per microliter, at each study time point. In addition, qualitative analyses will be carried out to investigate specific components of EV cargo that may be relevant to nerve injury and inflammation. These include selected classes of membrane lipids, such as phosphatidylcholine, sphingomyelin, and cholesterol, which are known to influence membrane stability and signaling, as well as microRNAs involved in neuronal function, stress responses, and neuroinflammatory pathways. The combination of quantitative and molecular profiling is intended to provide a multidimensional view of EV dynamics in relation to chemotherapy exposure.

Clinical evaluation of CIPN will be performed using validated symptom-based questionnaires and objective bedside tests of peripheral nerve function. These assessments capture both patient-reported experience and physician-based measures of sensory impairment, allowing a more comprehensive characterization of neurotoxicity than either approach alone. By relating EV-based measurements to these clinical data over time, the study will explore whether changes in EV concentration or composition precede, accompany, or follow the onset of neuropathic symptoms.

Individual susceptibility to CIPN is influenced by multiple factors, including demographic characteristics, pre-existing neuropathy, and genetic background. Although the primary focus of this study is on EV-derived biomarkers, relevant clinical and demographic information will be collected to allow exploratory analyses of how these factors may interact with EV patterns. This will help to distinguish EV changes that are primarily driven by chemotherapy-induced nerve damage from those that reflect underlying patient-specific characteristics.

Because the study does not modify or assign cancer treatments, all oncologic care will proceed according to standard clinical practice. The additional procedures introduced by the study are limited to blood sampling and non-invasive neurological assessments. These procedures are intended solely to support biomarker analysis and phenotypic characterization of CIPN and are not expected to interfere with therapeutic decisions or outcomes.

By focusing on EVs as circulating indicators of peripheral nerve injury, this study aims to generate data that may support the future development of minimally invasive tools for monitoring neurotoxicity in patients receiving chemotherapy. If specific EV-based patterns are found to be associated with CIPN, this could open the way to earlier identification of at-risk individuals and to more personalized management of neurotoxic side effects, with the ultimate goal of improving quality of life for cancer survivors.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Milan, Italy, 20122
        • Recruiting
        • SC Oncologia Medica Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Has signed the informed consent form
  • Is 18 years of age or older
  • Is male or female
  • Has breast cancer and is scheduled to receive paclitaxel, docetaxel, eribulin, capecitabine, or carboplatin as part of standard care
  • Has gastrointestinal cancer and is scheduled to receive oxaliplatin or capecitabine as part of standard care
  • Has lung cancer and is scheduled to receive cisplatin, carboplatin, or docetaxel as part of standard care
  • Has urologic cancer and is scheduled to receive carboplatin, cisplatin, paclitaxel, docetaxel, or enfortumab vedotin as part of standard care
  • Has head and neck cancer and is scheduled to receive carboplatin, paclitaxel, or cisplatin as part of standard care

Exclusion Criteria:

  • Has already been diagnosed with CIPN
  • Has a neurodegenerative disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Baseline (T0)
Patients eligible to receive antineoplastic compounds with taxanes, platinum compounds, or antimitotic agents, evaluated before the start of chemotherapy (baseline).
Procedure: CIPN assessment
Assessment of CIPN using a combination of physician-based and patient-reported measures. Objective evaluation includes assessment of vibration sensitivity. Patient-reported symptoms are assessed using the EORTC-CIPN20 questionnaire (Italian version), a 20-item self-administered questionnaire completed in approximately 10 minutes.
Other: EV blood analysis
Collection of blood samples for isolation, quantification, and molecular characterization of circulating EVs, including analysis of membrane lipid composition and microRNA content.
Other: End of Chemotherapy (T1)
Patients who have completed the planned chemotherapy cycles with taxanes, platinum compounds, or antimitotic agents and are evaluated at the end of treatment.
Procedure: CIPN assessment
Assessment of CIPN using a combination of physician-based and patient-reported measures. Objective evaluation includes assessment of vibration sensitivity. Patient-reported symptoms are assessed using the EORTC-CIPN20 questionnaire (Italian version), a 20-item self-administered questionnaire completed in approximately 10 minutes.
Other: EV blood analysis
Collection of blood samples for isolation, quantification, and molecular characterization of circulating EVs, including analysis of membrane lipid composition and microRNA content.
Other: Follow-up (T2)
Patients evaluated six months after completion of chemotherapy.
Procedure: CIPN assessment
Assessment of CIPN using a combination of physician-based and patient-reported measures. Objective evaluation includes assessment of vibration sensitivity. Patient-reported symptoms are assessed using the EORTC-CIPN20 questionnaire (Italian version), a 20-item self-administered questionnaire completed in approximately 10 minutes.
Other: EV blood analysis
Collection of blood samples for isolation, quantification, and molecular characterization of circulating EVs, including analysis of membrane lipid composition and microRNA content.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline in Circulating EV Concentration
Time Frame: 11 months from enrollment (T0), to completion of chemotherapy (T2)
Change in the concentration of circulating extracellular vesicles, expressed as vesicles per microliter of plasma, measured by comparing values at the end of chemotherapy (T1) and 6 months after completion of treatment (T2) with baseline at initiation of chemotherapy (T0), in relation to the development of chemotherapy-induced peripheral neuropathy. T1 corresponds to 5 months. T2 corresponds to 6 months after completion of treatment.
11 months from enrollment (T0), to completion of chemotherapy (T2)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from End of Chemotherapy in Circulating EV Concentration
Time Frame: 11 months from enrollment (T0), to completion of chemotherapy (T2)
Change in the concentration of circulating extracellular vesicles, expressed as vesicles per microliter of plasma, measured by comparing values at the end of chemotherapy (T1) and 6 months after completion of treatment (T2) with baseline at initiation of chemotherapy (T0), in relation to the development of chemotherapy-induced peripheral neuropathy. T1 corresponds to 5 months. T2 corresponds to 6 months after completion of treatment.
11 months from enrollment (T0), to completion of chemotherapy (T2)
Changes in EV Membrane Lipid Composition
Time Frame: 11 months from enrollment (T0), to completion of chemotherapy (T2)
The relative abundance of major EV membrane lipid classes-phosphatidylcholine, sphingomyelin, and cholesterol-will be quantified using targeted lipidomic analysis (e.g., mass spectrometry-based lipid profiling). Lipid levels will be expressed as mol (%) within EV samples collected at T0 (baseline), at the end of chemotherapy (T1 corresponding to 5 months) and at T2 (corresponding to 6 months after completion of treatment). Changes in lipid composition over time will be summarized descriptively and compared among time points (T1 vs T1 and T0 vs T2) to assess chemotherapy-associated alterations in EV membrane lipid profiles.
11 months from enrollment (T0), to completion of chemotherapy (T2)
Changes in Extracellular Vesicle microRNA Profile
Time Frame: 11 months from enrollment (T0), to completion of chemotherapy (T2)
Changes in the microRNA content of circulating extracellular vesicles measured at T0 (baseline), at the end of chemotherapy (T1 corresponding to 5 months from the initiation of chemotherapy) and at the end of chemotherapy (T2).
11 months from enrollment (T0), to completion of chemotherapy (T2)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Investigators

  • Study Chair: Ornella Garrone, MD, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
  • Principal Investigator: Massimiliano Ruscica, PhD, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2025

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

September 1, 2026

Study Registration Dates

First Submitted

January 19, 2026

First Submitted That Met QC Criteria

April 23, 2026

First Posted (Actual)

April 30, 2026

Study Record Updates

Last Update Posted (Actual)

April 30, 2026

Last Update Submitted That Met QC Criteria

April 23, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5648

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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