Effect of Exercise on Chemotherapy-Induced Peripheral Neuropathy (EX-CIPN)

A Randomized Controlled Trial Evaluating the Effects of Exercise on Chemotherapy-Induced Peripheral Neuropathy in Patients Treated With Oxaliplatin or Paclitaxel

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and often persistent adverse effect of oxaliplatin- and paclitaxel-based chemotherapy. While exercise is frequently recommended for patients with CIPN, it remains unclear whether exercise mitigates neuropathic injury itself or primarily improves physical function and quality of life.

This randomized controlled trial evaluates the effects of exercise on CIPN during and after chemotherapy. Patients receiving oxaliplatin for colorectal cancer or paclitaxel for gynecologic cancer are randomized to an exercise intervention or usual-care control. Neuropathy severity is assessed using objective neurophysiological measures, blood biomarkers, and validated clinical and patient-reported outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Peripheral Neuropathy, Secondary to Drugs or Chemicals; Paclitaxel Induced Neuropathy; Oxaliplatin Induced Peripheral Neuropathy in Cancer Patients
• Intervention / Treatment: Behavioral: Exercise Intervention; Other: Usual Care

Detailed Description

This is an open-label, randomized controlled trial conducted in patients undergoing neurotoxic chemotherapy. Two chemotherapy cohorts are included: patients receiving oxaliplatin-based chemotherapy for colorectal cancer and patients receiving paclitaxel-based chemotherapy for gynecologic cancer.

Participants are randomized 1:1 to an exercise intervention group or a usual-care control group. Randomization is performed prior to chemotherapy initiation, with stratification by age group and chemotherapy regimen to ensure balance between groups.

The exercise intervention consists of a structured home-based exercise program initiated at the start of chemotherapy and continued until three months after completion of chemotherapy. The program is designed to be safe and feasible during active cancer treatment, with adherence monitored through regular follow-up.

The primary objective is to determine whether exercise reduces the severity of chemotherapy-induced peripheral neuropathy, as assessed by objective neurophysiological testing and validated patient-reported measures. Secondary objectives include evaluation of blood biomarkers of neuroaxonal injury and inflammation, physical function, and quality of life.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Su-Hyun Kim, MD, PhD; Phone Number: 82-31-920-1683; Email: herena20@ncc.re.kr

Study Locations

• South Korea
  • Gyeonngi
    • Goyang, Gyeonngi, South Korea, 10408
      • National Cancer Center
      • Contact: Su-Hyun Kim,, MD, PhD; Phone Number: 82-31-920-1683; Email: herena20@ncc.re.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of colorectal cancer (oxaliplatin cohort) or gynecologic cancer (paclitaxel cohort)
• Planned initiation of oxaliplatin- or paclitaxel-based chemotherapy
• Karnofsky Performance Status ≥70
• Ability to provide written informed consent

Exclusion Criteria:

• Pre-existing peripheral neuropathy from other causes
• Severe comorbidities limiting safe participation in exercise
• Regular participation in a structured moderate- to high-intensity exercise program comparable to the study intervention prior to enrollment.
• Cognitive impairment interfering with study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise Intervention; Participants assigned to this arm will perform a structured home-based exercise program during chemotherapy and for up to three months after completion of chemotherapy. The exercise program is designed to be safe and feasible during active cancer treatment and includes aerobic and strengthening components. Participants receive standardized exercise education materials, and adherence and safety are monitored through regular telephone follow-up.	Behavioral: Exercise Intervention; A structured home-based exercise program performed during chemotherapy and for up to three months after completion of chemotherapy. The program includes aerobic and strengthening exercises and is designed to be safe and feasible during active cancer treatment. Adherence is monitored through regular telephone follow-up.
Active Comparator: Usual Care; Participants assigned to this arm will receive standard oncologic care and general education regarding chemotherapy-induced peripheral neuropathy. No structured exercise program is prescribed during the study period.	Other: Usual Care; Standard oncologic care and general education regarding chemotherapy-induced peripheral neuropathy, without a structured exercise program.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Chemotherapy-Induced Peripheral Neuropathy Severity (CTCAE v5.0)	Change in chemotherapy-induced peripheral neuropathy severity assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 sensory neuropathy grade (Grade 0-4, with higher grades indicating more severe neuropathy).	Baseline (prior to initiation of chemotherapy), end of chemotherapy (up to approximately 24 weeks after chemotherapy initiation), and 3 months after completion of chemotherapy.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Biomarkers	Serum neurofilament light chain (NfL), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), complement components (e.g., C5a), and inflammatory cytokines.	Baseline, end of chemotherapy, 3 months post-chemotherapy
Quality of Life Assessed by EORTC QLQ-C30	Quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). The questionnaire generates scores ranging from 0 to 100. For the global health status and functional scales, higher scores indicate better quality of life and functioning, whereas for symptom scales, higher scores indicate greater symptom burden.	Baseline, end of chemotherapy (up to approximately 24 weeks), and 3 months after completion of chemotherapy.
Change in Timed Up and Go Test Performance	Change in mobility and balance assessed using the Timed Up and Go (TUG) test, measured in seconds, with longer times indicating poorer performance.	Baseline (prior to initiation of chemotherapy), end of chemotherapy (up to approximately 24 weeks after chemotherapy initiation), and 3 months after completion of chemotherapy.
Change in Sensory Nerve Action Potential Amplitude	Change in sensory nerve action potential (SNAP) amplitude of predefined sensory nerves assessed by nerve conduction studies, measured in microvolts (µV), with lower amplitudes indicating greater axonal dysfunction.	Baseline (prior to initiation of chemotherapy), end of chemotherapy (up to approximately 24 weeks after chemotherapy initiation), and 3 months after completion of chemotherapy.
Change in Patient-Reported CIPN Symptoms Assessed by EORTC QLQ-CIPN20	Change in chemotherapy-induced peripheral neuropathy symptoms assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20-item scale (EORTC QLQ-CIPN20; score range 0-100, with higher scores indicating worse neuropathy).	Baseline, end of chemotherapy (up to approximately 24 weeks), and 3 months after completion of chemotherapy.
Change in Serum Neurofilament Light Chain Concentration	Change in serum neurofilament light chain (NfL) concentration, a biomarker of neuroaxonal injury, measured using a validated immunoassay.	Baseline (prior to initiation of chemotherapy), end of chemotherapy (up to approximately 24 weeks after chemotherapy initiation), and 3 months after completion of chemotherapy.
Change in Serum Brain-Derived Neurotrophic Factor Level	Change in serum brain-derived neurotrophic factor (BDNF) level, measured using a single molecule array (SIMOA) immunoassay.	Baseline, end of chemotherapy (up to approximately 24 weeks), and 3 months after completion of chemotherapy.
Change in Serum Complement Component C5a Level	Change in serum complement component C5a level, a marker of complement activation, measured using the MicroVue™ C5a enzyme immunoassay.	Baseline (prior to initiation of chemotherapy), end of chemotherapy (up to approximately 24 weeks after chemotherapy initiation), and 3 months after completion of chemotherapy.
Change in Sit-to-Stand Test Performance	Change in lower extremity functional strength assessed using the Sit-to-Stand test, measured as time to complete the test or number of repetitions, as applicable.	Baseline, end of chemotherapy (up to approximately 24 weeks), and 3 months after completion of chemotherapy.
Change in 2-Minute Walk Test Distance	Change in functional exercise capacity assessed using the 2-Minute Walk Test, measured as total distance walked in meters.	Baseline, end of chemotherapy (up to approximately 24 weeks), and 3 months after completion of chemotherapy.
Change in Handgrip Strength	Change in upper extremity muscle strength assessed using handgrip dynamometry, measured in kilograms, with lower values indicating reduced strength.	Baseline, end of chemotherapy (up to approximately 24 weeks), and 3 months after completion of chemotherapy.
Secondary Outcome: Sensory Nerve Conduction Velocity	Change in sensory nerve conduction velocity of predefined sensory nerves assessed by nerve conduction studies, measured in meters per second (m/s), with lower velocities indicating greater demyelination or conduction slowing.	Baseline (prior to initiation of chemotherapy), end of chemotherapy (up to approximately 24 weeks after chemotherapy initiation), and 3 months after completion of chemotherapy.
Change in Serum Nerve Growth Factor Level	Change in serum nerve growth factor (NGF) level, measured using a validated immunoassay.	Baseline, end of chemotherapy (up to approximately 24 weeks after chemotherapy initiation), and 3 months after completion of chemotherapy.
Change in Circulating Inflammatory Cytokine Levels	Change in circulating levels of selected pro- and anti-inflammatory cytokines measured using a multiplex enzyme-linked immunosorbent assay.	Baseline, end of chemotherapy (up to approximately 24 weeks), and 3 months after completion of chemotherapy.

Collaborators and Investigators

• Sponsor: National Cancer Center, Korea

Study record dates

Study Major Dates

• Study Start (Estimated): February 3, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: January 18, 2026
• First Submitted That Met QC Criteria: February 2, 2026
• First Posted (Actual): February 10, 2026

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Exercise; CIPN; chemotherapy induced peripheral neuropathy
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Behavior; Peripheral Nervous System Diseases; Motor Activity
• Other Study ID Numbers: NCC-CIPN-EX-2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the results reported in the manuscript.
• IPD Sharing Time Frame: Beginning 6 months after publication of the primary results and ending 5 years after publication.
• IPD Sharing Access Criteria: Individual participant data will be shared upon reasonable request. Requests must include a methodologically sound proposal and be approved by the study investigators. Data will be shared after execution of a data sharing agreement, in accordance with institutional policies and applicable regulations.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No