Chemotherapy Induced Peripheral Neuropathy, Chemotherapy Induced Peripheral Neuropathy (CIPN), CIPN, CIPN - Chemotherapy-Induced Peripheral Neuropathy, CIPN in Adjuvant Breast Cancer Patients
Conditions
Keywords
CIPN, Cryotherapy, TNSn score, multimodal assessment, breast cancer, paclitaxel weekly
Brief summary
Female breast cancer patients receiving weekly paclitaxel-based chemotherapy are at risk of developing chemotherapy-induced peripheral neuropathy (CIPN), which may negatively affect quality of life and lead to treatment modifications or discontinuation. The aim of this clinical trial is to evaluate whether acral cryotherapy during chemotherapy administration can reduce the incidence and severity of CIPN. Participants receiving cryotherapy will be compared with participants receiving standard care without cryotherapy. During chemotherapy treatment and throughout the first year of follow-up, all participants will undergo serial evaluations of peripheral nerve function, including neurological examinations, nerve conduction studies, patient-reported quality-of-life questionnaires, and blood tests. In addition to routine laboratory testing, extra blood samples will be collected at two time points to assess biomarkers of nerve damage.
Detailed description
Female breast cancer patients receiving weekly paclitaxel-based chemotherapy are at risk of developing chemotherapy-induced peripheral neuropathy (CIPN), a frequent and potentially dose-limiting toxicity caused by damage to peripheral nerves. Symptoms of CIPN may persist long after treatment completion and can significantly impair quality of life and daily functioning. The application of cold to the hands and feet during chemotherapy administration may reduce the incidence and severity of CIPN by decreasing local blood flow and limiting exposure of peripheral nerves to chemotherapy agents. The aim of this study is to evaluate whether continuous-flow cryotherapy at 15°C during weekly paclitaxel administration can reduce the incidence and severity of CIPN in breast cancer patients. Participants receiving continuous-flow cryotherapy will be compared with participants receiving standard care without cryotherapy. During chemotherapy treatment and throughout the first year of follow-up, all participants will undergo serial assessments of peripheral nerve function, including neurological examinations, nerve conduction studies, patient-reported quality-of-life questionnaires, and laboratory testing. In addition to routine blood tests, extra blood samples will be collected at two time points to assess biomarkers associated with nerve damage.
Interventions
DEVICECryotherapy
Hilotherm Chemocare™ is a dedicated cryotherapy device designed for the prevention of chemotherapy-induced peripheral neuropathy (CIPN) in patients receiving neurotoxic chemotherapy. The system consists of a closed-loop circulation unit through which a temperature-controlled cooling medium is delivered to specially designed cuffs applied to the hands and feet. A processor-controlled system maintains a stable and continuous temperature throughout the treatment session. For CIPN prevention, the manufacturer-recommended target temperature is set at 15°C. Cryotherapy will be administered starting 15 minutes before the initiation of chemotherapy infusion, continued throughout the entire duration of chemotherapy administration, and maintained for 15 minutes after completion of the infusion.
Sponsors
Azienda Sanitaria dell'Alto Adige
University of Milano Bicocca
Paracelsus Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Paclitaxel weekly (80 mg/m2) at least 12 cycles (in adjuvant, neo-adjuvant setting or metastatic setting following the present schemes: TH (Paclitaxel, Trastuzumab), AC-TH (Doxorubicin, Cyclophosphamide, Paclitaxel, Trastuzumab), AC-THP (Doxorubicin, Cyclophosphamide, Paclitaxel, Trastuzumab, Pertuzumab), AC-T (Doxorubicin, Cyclophosphamide, Paclitaxel) * Eastern Cooperative Oncology Group Performance Status (ECOG) \< 2 * Female sex * Age: 18-90 years * written informed consent
Exclusion criteria
* pre-existing motor/sensitive peripheral neuropathy * diabetes * Endocrinopathies * presence of brain, bone, soft tissue, or skin of hands or feet metastases * Raynaud's syndrome * Peripheral arterial disease * hand and foot syndrome * any other reason that may hamper the data collection as assessed by the examiner
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Total Neuropathy Score-Nurse Version (TNSn) | Baseline (before the first paclitaxel infusion) and 6 months after completion of paclitaxel treatment (approximately 9 months from baseline) | The Total Neuropathy Score-Nurse Version (TNSn) is a clinician-administered composite measure of chemotherapy-induced peripheral neuropathy. It comprises 5 items (sensory symptoms, motor symptoms, autonomic symptoms, pin-prick sensibility and vibration sensibility), each scored from 0 to 4 and summed to yield a total score ranging from 0 (minimum, no neuropathy) to 20 (maximum, most severe neuropathy); higher scores indicate a worse outcome. For each participant, the change from baseline is calculated as the TNSn total score at 6 months after completion of chemotherapy minus the TNSn total score at baseline. Positive values indicate worsening of neuropathy. The outcome is summarized per arm as the mean change with standard deviation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Peak-to-Peak Amplitude of the Dorsal Sural Sensory Nerve Action Potential (µV) | Baseline (before the first paclitaxel infusion), and 3, 6 and 12 months after completion of paclitaxel treatment (up to approximately 15 months from baseline) | Peak-to-peak amplitude of the dorsal sural sensory nerve action potential (SNAP), measured in microvolts (µV) by sensory nerve conduction study on the non-dominant lower limb with surface electrodes (2-channel EMG). For each participant, the change from baseline is calculated at each post-baseline time point as the amplitude at that time point minus the baseline amplitude. Negative values indicate a decrease in amplitude compared with baseline; lower amplitudes indicate greater sensory nerve dysfunction (axonal loss). The outcome is summarized per arm as the mean change with standard deviation. . |
| Mean Change From Baseline in Serum Neurofilament Light Chain (NfL) Concentration (pg/mL) | Baseline (before the first paclitaxel infusion), mid-chemotherapy (cycle 6, approximately 6 weeks) | Serum neurofilament light chain (NfL) concentration, measured in pg/mL by single-molecule array (Simoa) immunoassay as a biomarker of neuroaxonal damage. For each participant, the change from baseline is calculated as the post-baseline value minus the baseline value. Higher concentrations indicate greater neuroaxonal injury. The outcome is summarized per arm as the mean change with standard deviation. |
| Mean Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) Subscale Score | Baseline, cycles 3, 6, 8, 10 and 12 (approximately 3, 6, 8, 10 and 12 weeks), and 3, 6 and 12 months after completion of paclitaxel treatment (up to approximately 15 months from baseline) | The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) subscale is a validated patient-reported questionnaire assessing chemotherapy-induced neurotoxicity. It comprises 11 items, each rated from 0 to 4 and scored according to the FACIT manual to yield a subscale score ranging from 0 (minimum) to 44 (maximum); lower scores indicate more severe neurotoxicity (worse outcome) and higher scores indicate fewer symptoms (better outcome). For each participant, the change from baseline is calculated at each post-baseline time point as the subscale score at that time point minus the score at baseline. Negative values indicate worsening of patient-reported neurotoxicity. The outcome is summarized per arm as the mean change with standard deviation. |
Countries
Italy
Contacts
CONTACTMattia Bergamo, MD
STUDY_CHAIRSonia Prader, MD
Azienda Sanitaria dell'Alto Adige
Outcome results
None listed