## Protocol Section
### Identification Module
**NCT ID:** NCT06430814

**Brief Title:** Clinical Biomarker of Paclitaxel-induced Peripheral Neuropathy

**Official Title:** Clinical Biomarker of Paclitaxel-induced Peripheral Neuropathy

#### Organization Study ID Info
**ID:** AKF-403
#### Organization
**Class:** OTHER
**Full Name:** University of Southern Denmark
### Status Module
#### Completion Date
**Date:** 2026-09

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-28

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-23

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-09

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-09

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-28
**Type:** ACTUAL
**Study First Submit Date:** 2024-04-25
**Study First Submit QC Date:** 2024-05-23
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Odense University Hospital

**Class:** OTHER

**Name:** Sygehus Lillebaelt

**Class:** UNKNOWN

**Name:** Esbjerg Hospital

**Class:** OTHER_GOV

**Name:** Sonderborg Hospital

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Southern Denmark

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Chemotherapy-induced Peripheral Neuropathy

### Design Module

#### Bio Spec

**Description:** The investigators are taking blood samples to analyze the NFL level, paclitaxel concentration, and looking at DNA sequencing associated with PIPN. The investigators will also take skin biopsies to look at the nerve fiber density and if gene and protein expression of relevant genes changes following paclitaxel treatment.

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 188

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

- Other: No intervention

**Label:** Breastcancer patients

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Breastcancer patients

**Description:** No intervention

**Name:** No intervention

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** NFL level correlation

**Time Frame:** Before treatment start and during four cycles (one cycle equals 3 weeks)

#### Secondary Outcomes

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

**Measure:** Paclitaxel exposure

**Time Frame:** Before treatment start and during four cycles (one cycle equals 3 weeks)

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

**Measure:** Genes and PIPN

**Time Frame:** Before treatment start and during four cycles (one cycle equals 3 weeks)

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

**Measure:** Genes and NFL

**Time Frame:** Before treatment start and during four cycles (one cycle equals 3 weeks)

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

**Measure:** Genes and Paclitaxel

**Time Frame:** Before treatment start and during four cycles (one cycle equals 3 weeks)

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

**Measure:** Drug-drug interactions

**Time Frame:** Before treatment start and during four cycles (one cycle equals 3 weeks)

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

**Measure:** Skin biopsies

**Time Frame:** Before treatment start and during four cycles (one cycle equals 3 weeks)

**Description:** 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.

**Measure:** IENFD

**Time Frame:** Before treatment start and during four cycles (one cycle equals 3 weeks)

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

**Measure:** PHS

**Time Frame:** Before treatment start and during four cycles (one cycle equals 3 weeks)

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

**Measure:** Nerve fiber dysfunction

**Time Frame:** Before treatment start and during four cycles (one cycle equals 3 weeks)

### Eligibility Module

**Eligibility Criteria:** 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

**Minimum Age:** 18 Years

**Sampling Method:** PROBABILITY_SAMPLE

**Sex:** FEMALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

**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.

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** dbiversen@health.sdu.dk

**Name:** Ditte Bork Iversen, MSc Pharm, PhD

**Phone:** +45 65 50 23 52

**Role:** CONTACT

**Contact 2:**

**Email:** tstage@health.sdu.dk

**Name:** Tore B. Stage, Prof

**Phone:** +45 65 50 36 78

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** University of Southern Denmark

**Name:** Ditte Bork Iversen

**Role:** STUDY_CHAIR

### IPD Sharing Statement Module

**Description:** Data on individual participants is not allowed due to GDPR

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009468

- Term: Neuromuscular Diseases

- ID: D000009422

- Term: Nervous System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M13432

- Name: Peripheral Nervous System Diseases

- Relevance: HIGH

- As Found: Peripheral Neuropathy

- ID: M12411

- Name: Neuromuscular Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000010523

- Term: Peripheral Nervous System Diseases

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M19537

- Name: Paclitaxel

- Relevance: LOW

- As Found: Unknown

- ID: M231

- Name: Albumin-Bound Paclitaxel

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
