Chemotherapy-induced Peripheral Neuropathy
Conditions
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.
Interventions
OTHERNo intervention
No intervention
Sponsors
Odense University Hospital
Sygehus Lillebaelt
Sonderborg Hospital
University of Southern Denmark
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NFL level correlation | Before 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
| Measure | Time frame | Description |
|---|---|---|
| Genes and PIPN | Before 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. |
| Genes and NFL | Before 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 Paclitaxel | Before 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. |
| Drug-drug interactions | Before treatment start and during four cycles (one cycle equals 3 weeks) | Investigate if and which specific drug-drug interactions are correlated to developing PIPN. |
| Paclitaxel exposure | Before 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 |
| IENFD | Before 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. |
| PHS | Before 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. |
| Nerve fiber dysfunction | Before 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. |
| Skin biopsies | Before 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. |
Countries
Denmark
Contacts
Primary ContactDitte Bork Iversen, MSc Pharm, PhD
Backup ContactTore B. Stage, Prof
Outcome results
None listed