Chemotherapy-Induced Peripheral Neuropathy - Additional Evaluation in Breast Cancer Survivors (NEURO-BREAC-02)

Chemotherapy-induced Peripheral Neuropathy - Additional Evaluation of a Self-administered Scoring System for Breast Cancer Survivors

The main goal of this trial is to identify the optimal cut-off score of a Scoring System to discriminate between mild chemotherapy-induced peripheral neuropathy (CIPN) and no CIPN in breast cancer survivors previously treated with taxane-based chemotherapy and adjuvant radiotherapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Diagnostic test: Symptom-based scoring system

Detailed Description

Adjuvant radiotherapy is a standard procedure following breast-conserving surgery for non-metastatic breast cancer. Depending of the tumor stage and other risk factors, radiotherapy may be indicated also after mastectomy. A considerable number of these patients receive pre- or postoperative chemotherapy. These regimens generally include taxanes (paclitaxel or docetaxel), which are known to be associated with a considerable risk of chemotherapy-induced peripheral neuropathy (CIPN). CIPN can be quite burdensome for the affected patients. According to three review articles, there is no effective prophylactic treatment to prevent peripheral neuropathy (PNP) in general. Moreover, treatment options for existing PNP are limited. The only agent shown to be effective to improve symptoms of PNP in a phase 3 trial is duloxetine, a serotonin an nor-epinephrine dual uptake inhibitor. In addition, physiotherapy may contribute to maintaining or improving the patient's gait function. Close monitoring during the treatment is important to be able to adapt the regimen of neurotoxic chemotherapy very soon after the first symptoms of CIPN occur. To prevent severe neurotoxicity during chemotherapy, the oncology service needs to follow early development of symptoms. In breast cancer patients treated with taxanes, dose reduction due to early development of neuropathy did not change long-term outcomes of toxicity symptoms, suggesting that responses to first doses might be important. In addition, the patient and service burden prohibit frequent out-patient visits to have early detection of toxicity. In clinical neurotoxicity studies a great effort has been put into documenting the validity of grading scales incorporating results from clinical examination with the symptom results. Both approaches require health care resources to document and follow up on CIPN development in order to intervene in the case of severe early toxicity. A scoring system has been developed by members of our group, which is based on patient reported symptoms and signs from self-examination. Depending on number and severity of symptoms identified by the study participants themselves (self-assessment) with the help of a neuropathy tracker, a score ranging between 0 and 44 points is obtained. In a preceding prospective trial, it was shown that the new scoring system can contribute to the identification of moderate to severe CIPN in breast cancer patients who had received taxane-based chemotherapy.

The main goal of this trial is to identify the optimal cut-off score of a scoring system to discriminate between mild CIPN and no CIPN in breast cancer survivors previously treated with taxane-based chemotherapy and adjuvant radiotherapy. To identify the optimal cut-off score of a scoring system to discriminate between mild CIPN and no CIPN in breast cancer survivors previously treated with taxane-based chemotherapy and adjuvant radiotherapy. The scores that range between 0 and 44 points are obtained by using a neuropathy tracker. This tracker is based on self-evaluation of symptoms and signs of CIPN by the study participants. The receiver operating characteristic (ROC) curve is used to show the connection between sensitivity and specificity for every possible cut-off for the Scoring System and select the optimal scoring point for detection of mild CIPN. Secondary aims include satisfaction of the study participants with the scoring system and identification of an optimal cut-off score for the Utah Early Neuropathy Scale to discriminate between mild CIPN and no CIPN.

Sample size calculation: The main goal of this trial is to identify the optimal cut-off score of a scoring system to discriminate between mild CIPN and no CIPN in breast cancer survivors. The discriminative power of the Scoring System will be assessed by calculating the area under the receiver operating characteristic (ROC) curve (AUC). Sample size is calculated to achieve acceptable precision in the estimation of the AUC measured by means of the 90% confidence interval by incorporating a pre-specified probability, which is referred to as assurance, of achieving the desired lower confidence limit. The following assumptions are made:

• The two-sided significance level is set to 10%
• An AUC of 0.95 is assumed since this is decided to be an excellent diagnostic accuracy for the Scoring System worth to be considered for future routine use.
• The pre-specified lower bound of the confidence interval is assumed to be 0.7.
• The assurance probability is set to 80%.
• The ratio of standard deviations in patients with no CIPN and patients with mild CIPN is assumed to be 0.67.
• Approximately 25% of the patients to be included in this study will have no CIPN (according to standard physical examination and medical history), whereas the other 75% will be clinically diagnosed with mild CIPN, i.e. ratio between negative and positive cases is approximately 0.33.

Based on these assumptions above, 26 patients (19 with mild CIPN and 7 without CIPN) are required within the Full Analysis Set. Assuming that roughly 5% of patients will not qualify for Full Analysis Set, a total of 28 patients should be enrolled in the NEURO-BREAC-02 trial.

The Full Analysis Set includes all patients who completed the self-assessment of CIPN.

Statistical considerations: All data recorded in the case report forms describing the study population (demographic and clinical characteristics recorded at baseline), rates of mild CIPN, and safety will be analyzed descriptively. Categorical data will be presented in contingency tables with frequencies and percentages. Continuous data will be summarized with at least the following: frequency, median, quartiles, mean, standard deviation (standard error), minimum and maximum. Number of patients with protocol deviations during the study and listings describing the deviations will be provided. The data analysis will be performed according to the statistical analysis plan (SAP), and which will be finalized prior to database lock and prior to any statistical analysis.

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dirk Rades, Prof. Dr. med., FASTRO; Phone Number: 45400 0049-451500; Email: Dirk.Rades@uksh.de
• Study Contact Backup: Name: Maria K Streubel, Dr. rer. nat.; Phone Number: 45420 0049-451500; Email: MariaKarolin.Streubel@uksh.de

Study Locations

• Germany
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23562
      • Department of Radiation Oncology, University of Luebeck
      • Contact: Dirk Rades, Prof. Dr. med., FASTRO; Phone Number: 45400 0049-451500; Email: Dirk.Rades@uksh.de
      • Contact: Maria K Streubel, Dr. rer. nat.; Phone Number: 45420 0049.451-500

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Histologically proven breast cancer
2. Previous treatment with taxane-based chemotherapy followed by adjuvant radiotherapy
3. Mild or no CIPN according to the Total Neuropathy Score
4. Female gender
5. Age ≥18 years
6. Written informed consent
7. Capacity of the patient to consent

Exclusion Criteria:

1. Disease-related skin disorders of the lower extremities (e.g., related to skin infections, bullous dermatoses, dermatitis, papulo-squamous skin disorders, or urticaria/erythema)
2. Pregnancy, Lactation
3. Expected non-compliance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Breast cancer patients treated with taxane-base chemotherapy; Patients who were previously treated with taxane-base chemotherapy and adjuvant radiotherapy for breast cancer and developed either no or mild chemotherapy-induced peripheral neuropathy

Diagnostic test: Symptom-based scoring system; The patients will be asked to complete the self-evaluation of symptoms and signs of neuropathy using a Neuropathy Tracker that questions symptoms quality, severity and distribution and guide the user through a systematic evaluation of pin-prick from a needle and vibration from the mobile on successive levels from the toes to the knee on both legs. Finally, the extension force or both great toes will be self-assessed by the participant. The self-examination is based on the structure of the Utah Early Neuropathy Score.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with mild chemotherapy-induced peripheral neuropathy	Chemotherapy-induced peripheral neuropathy will be assessed with a symptom-based scoring system supported by a neuropathy tracker.	from enrollment to clinical examination at 1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of patient satisfaction	Patient satisfaction with the symptom-based scoring system ranging from 0 to 44 points (higher scores represent a higher grade of peripheral neuropathy) will be assessed using a specific questionnaire.	from enrollment to clinical examination at 1 week
Number of participants with mild chemotherapy-induced peripheral neuropathy according to the Utah Early Neuropathy Scale	Chemotherapy-induced peripheral neuropathy will be assessed with a symptom-based scoring system using the Utah Early Neuropathy Scale.	from enrollment to clinical examination at 1 week

Collaborators and Investigators

• Sponsor: University Hospital Schleswig-Holstein
• Investigators: Principal Investigator: Dirk Rades, Prof. Dr. med., FASTRO, University of Luebeck, Germany

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: May 17, 2026
• First Submitted That Met QC Criteria: May 17, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 17, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Breast cancer; Chemotherapy; Chemotherapy-induced peripheral neuropathy; Taxanes; Scoring system
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: NEURO-BREAC-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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