Clinical Biomarker of Paclitaxel-induced Peripheral Neuropathy

Investigation of which patients treated with paclitaxel have an increased risk of developing peripheral neuropathy.

Study Overview

• Status: Recruiting
• Conditions: Chemotherapy-induced Peripheral Neuropathy
• Intervention / Treatment: Other: No intervention

Detailed Description

The primary aim of this study is to validate the protein neurofilament light chain (NFL) as a biomarker of the side effect paclitaxel-induced peripheral neuropathy (PIPN) and its utility in predicting this side effect in patients with breast cancer. The investigators want to include 188 patients at four different trial sites. The patients must follow their normal treatment cycles while getting blood drawn during their treatment period however maximal 4 cycles.

Blood samples are dawn before treatment initiation and once before each new cycle start in order to measure neurofilament light chain (NFL) before and during treatment. The investigators also want to take a skin biopsy before treatment start and after either cycle 3 or 4.

The primary endpoint of the study is if serum NFL>100 pg/ml after first cycle of paclitaxel can predict early termination of paclitaxel due to peripheral neuropathy.

• Study Type: Observational
• Enrollment (Estimated): 188

Contacts and Locations

• Study Contact: Name: Ditte Bork Iversen, MSc Pharm, PhD; Phone Number: +45 65 50 23 52; Email: dbiversen@health.sdu.dk
• Study Contact Backup: Name: Tore B. Stage, Prof; Phone Number: +45 65 50 36 78; Email: tstage@health.sdu.dk

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Recruiting
    • Odense University Hospital
    • Contact: Marianne Vogsen; Phone Number: +4550932282; Email: marianne.vogsen@rsyd.dk
  • Sønderborg, Denmark, 6400
    • Recruiting
    • University Hospital of Southern Denmark, Sønderborg
    • Contact: Marianne Christensen; Phone Number: +4579973034; Email: marianne.christensen.onk@rsyd.dk
  • Vejle, Denmark, 7100
    • Recruiting
    • University Hospital of Southern Denmark, Vejle
    • Contact: Lise Ventzel; Phone Number: +4579406060; Email: lise.ventzel@rsyd.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

A total of 188 patients diagnosed with breast cancer who are scheduled for paclitaxel treatment, either as adjuvant or neo-adjuvant treatment, will be recruited across four trial sites.

Description

Inclusion Criteria:

• Age > 18 years
• Willing to give informed consent
• Scheduled to receive neo-adjuvant or adjuvant paclitaxel treatment
• Able to speak and understand Danish
• Diagnosed with breast cancer
• Paclitaxel naïve patients

Exclusion Criteria:

• Neurodegenerative diseases (e.g., neuropathy from another cause, previous apoplexy, disc herniation
• Type 1 or 2 diabetes
• Pregnant
• Breastfeeding
• Relapse of cancer diagnosis
• Diagnosed with human immunodeficiency virus (HIV)
• Participation in other clinical trials where the dose of paclitaxel is changed, or the aim is to prevent neuropathic pain or decrease NFL level (except if the intervention is to use cooling gloves).
• Previous treatment with neurotoxic chemotherapy
• Chronic pain from another cause
• Metastatic cancer

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Breastcancer patients; A total of 188 patients diagnosed with breast cancer who are scheduled for paclitaxel treatment, either as adjuvant or neo-adjuvant treatment, will be recruited across three trial sites.	Other: No intervention; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NFL level correlation	The primary endpoint of the study is if serum NFL>100 pg/ml after first cycle (one cycle equals 3 weeks) of paclitaxel can predict early termination of paclitaxel due to peripheral neuropathy.	Before treatment start and during four cycles (one cycle equals 3 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Paclitaxel exposure	To measure if high concentration of paclitaxel exposure is correlated to high NFL level in blood	Before treatment start and during four cycles (one cycle equals 3 weeks)
Genes and PIPN	To measure if genetic variants in genes (e.g., CYP2C8*3, EPHA4/5, FGD4) are associated with more server PIPN symptoms.	Before treatment start and during four cycles (one cycle equals 3 weeks)
Genes and NFL	To measure if genetic variants in genes (e.g., CYP2C8*3, EPHA4/5, FGD4) are associated with high NFL concentration in blood.	Before treatment start and during four cycles (one cycle equals 3 weeks)
Genes and Paclitaxel	To measure if genetic variants in genes (e.g., CYP2C8*3, EPHA4/5, FGD4) are associated with high paclitaxel concentration in blood.	Before treatment start and during four cycles (one cycle equals 3 weeks)
Drug-drug interactions	Investigate if and which specific drug-drug interactions are correlated to developing PIPN.	Before treatment start and during four cycles (one cycle equals 3 weeks)
Skin biopsies	Obtain skin biopsies from patients to elucidate which molecular mechanisms and phenotypes are associated with PIPN.	Before treatment start and during four cycles (one cycle equals 3 weeks)
IENFD	Obtain skin biopsies at baseline and at the beginning of cycle 3 or 4 (one cycle equals 3 weeks) to assess if the intraepidermal nerve fiber density (IENFD) changes during paclitaxel treatment.	Before treatment start and during four cycles (one cycle equals 3 weeks)
PHS	To assess whether the patients who have a sensation of heat during cooling of the skin (PHS) are also those who experience neuropathic pain.	Before treatment start and during four cycles (one cycle equals 3 weeks)
Nerve fiber dysfunction	To examine if increased NFL level is correlated to changes in small and large nerve fibers dysfunction.	Before treatment start and during four cycles (one cycle equals 3 weeks)

Collaborators and Investigators

• Sponsor: University of Southern Denmark
• Collaborators: Odense University Hospital; Sygehus Lillebaelt; Sonderborg Hospital
• Investigators: Study Chair: Ditte Bork Iversen, University of Southern Denmark

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: April 25, 2024
• First Submitted That Met QC Criteria: May 23, 2024
• First Posted (Actual): May 28, 2024

Study Record Updates

• Last Update Posted (Estimated): September 2, 2025
• Last Update Submitted That Met QC Criteria: August 25, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases
• Other Study ID Numbers: AKF-403

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data on individual participants is not allowed due to GDPR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No