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.
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
pre-existing motor/sensitive peripheral neuropathy
diabetes
Endocrinopathies
presence of brain, bone, soft tissue, or skin of hands or feet metastases
Parallel
Cryotherapy
DeviceHilotherm 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.
Mean Change From Baseline in Total Neuropathy Score-Nurse Version (TNSn)
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.
Mean Change From Baseline in Peak-to-Peak Amplitude of the Dorsal Sural Sensory Nerve Action Potential (µV)
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)
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
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.
Mean Change From Baseline in Peak-to-Peak Amplitude of Sensory Nerve Action Potentials (microvolts)
Peak-to-peak amplitude of sensory nerve action potentials (SNAP), measured in microvolts (uV) by sensory nerve conduction study on the non-dominant side with surface electrodes (2-channel EMG). For each participant and each nerve, 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. Results will be reported separately for each nerve assessed (sural nerve, ulnar nerve). The outcome is summarized per arm as the mean change with standard deviation.
Mean Change From Baseline in Peak-to-Peak Amplitude of Compound Muscle Action Potentials (millivolts)
Peak-to-peak amplitude of compound muscle action potentials (CMAP), measured in millivolts (mV) by motor nerve conduction study on the non-dominant side with surface electrodes (2-channel EMG). For each participant and each nerve, 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 motor nerve dysfunction. Results will be reported separately for each nerve assessed (peroneal nerve, ulnar nerve). The outcome is summarized per arm as the mean change with standard deviation.
Mean Change From Baseline in Sensory Nerve Conduction Velocity (m/s)
Sensory nerve conduction velocity, measured in metres per second (m/s) by sensory nerve conduction study on the non-dominant side with surface electrodes (2-channel EMG). For each participant and each nerve, the change from baseline is calculated at each post-baseline time point as the conduction velocity at that time point minus the baseline velocity. Negative values indicate slowing of conduction compared with baseline; lower velocities indicate greater sensory nerve dysfunction. Results will be reported separately for each nerve assessed (dorsal sural nerve, sural nerve, ulnar nerve). The outcome is summarized per arm as the mean change with standard deviation.
Mean Change From Baseline in Motor Nerve Conduction Velocity (m/s)
Motor nerve conduction velocity, measured in metres per second (m/s) by motor nerve conduction study on the non-dominant side with surface electrodes (2-channel EMG). For each participant and each nerve, the change from baseline is calculated at each post-baseline time point as the conduction velocity at that time point minus the baseline velocity. Negative values indicate slowing of conduction compared with baseline; lower velocities indicate greater motor nerve dysfunction. Results will be reported separately for each nerve assessed (peroneal nerve, ulnar nerve). The outcome is summarized per arm as the mean change with standard deviation.
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Azienda Sanitaria dell'Alto Adige
Lead sponsor
University of Milano Bicocca
Collaborator
Paracelsus Medical University
Collaborator
