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Clinical Biomarker of Paclitaxel-induced Peripheral Neuropathy

Recruiting
Conditions
Chemotherapy-induced Peripheral Neuropathy
Interventions
Other: No intervention
Registration Number
NCT06430814
Lead Sponsor
University of Southern Denmark
Brief Summary

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

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
188
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Breastcancer patientsNo interventionA 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.
Primary Outcome Measures
NameTimeMethod
NFL level correlationBefore treatment start and during four cycles (one cycle equals 3 weeks)

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.

Secondary Outcome Measures
NameTimeMethod
Genes and NFLBefore treatment start and during four cycles (one cycle equals 3 weeks)

To measure if genetic variants in genes (e.g., CYP2C8\*3, EPHA4/5, FGD4) are associated with high NFL concentration in blood.

Genes and PaclitaxelBefore treatment start and during four cycles (one cycle equals 3 weeks)

To measure if genetic variants in genes (e.g., CYP2C8\*3, EPHA4/5, FGD4) are associated with high paclitaxel concentration in blood.

IENFDBefore treatment start and during four cycles (one cycle equals 3 weeks)

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.

Paclitaxel exposureBefore treatment start and during four cycles (one cycle equals 3 weeks)

To measure if high concentration of paclitaxel exposure is correlated to high NFL level in blood

Skin biopsiesBefore treatment start and during four cycles (one cycle equals 3 weeks)

Obtain skin biopsies from patients to elucidate which molecular mechanisms and phenotypes are associated with PIPN.

PHSBefore treatment start and during four cycles (one cycle equals 3 weeks)

To assess whether the patients who have a sensation of heat during cooling of the skin (PHS) are also those who experience neuropathic pain.

Genes and PIPNBefore treatment start and during four cycles (one cycle equals 3 weeks)

To measure if genetic variants in genes (e.g., CYP2C8\*3, EPHA4/5, FGD4) are associated with more server PIPN symptoms.

Drug-drug interactionsBefore treatment start and during four cycles (one cycle equals 3 weeks)

Investigate if and which specific drug-drug interactions are correlated to developing PIPN.

Nerve fiber dysfunctionBefore treatment start and during four cycles (one cycle equals 3 weeks)

To examine if increased NFL level is correlated to changes in small and large nerve fibers dysfunction.

Trial Locations

Locations (3)

Odense University Hospital

🇩🇰

Odense, Denmark

University Hospital of Southern Denmark, Sønderborg

🇩🇰

Sønderborg, Denmark

University Hospital of Southern Denmark, Vejle

🇩🇰

Vejle, Denmark

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