Continuous Controlled Cooling for Prevention of Chemotherapy-Induced Peripheral Neuropathy (COOL-tax)

Continuous Controlled Cooling for Prevention of Chemotherapy Induced Peripheral Neuropathy: A Randomized Controlled Trial

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of certain types of chemotherapy and can cause numbness, tingling, pain, and other symptoms in the hands and feet. There is currently no established method for preventing CIPN.

The purpose of this randomized controlled trial is to investigate whether continuous, controlled cooling of the hands and feet during chemotherapy can reduce the development and severity of CIPN. Participants will be randomly assigned to receive either cooling with the Hilotherm device during chemotherapy or standard care without cooling.

The study will compare peripheral neuropathy between the two groups and assess whether continuous cooling can help prevent chemotherapy-induced peripheral neuropathy.

Study Overview

• Status: Not yet recruiting
• Conditions: Chemotherapy Induced Peripheral Neuropathy (CIPN)
• Intervention / Treatment: Device: Continuous Controlled Cooling of the Hands and Feet

Detailed Description

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially long-lasting adverse effect of taxane-based chemotherapy. Currently, there is no established preventive treatment for CIPN. Previous studies of cooling interventions have shown promising results, but the available evidence remains limited.

The proposed mechanism of cooling is cold-induced vasoconstriction, which may reduce peripheral exposure to neurotoxic chemotherapy agents. Conventional cryotherapy using frozen gloves and socks has practical limitations, including fluctuating temperatures, frequent replacement, patient discomfort, and increased workload for healthcare personnel. Continuous cooling with hilotherapy provides stable temperature control and may therefore offer a more tolerable and feasible approach.

This study will evaluate whether hilotherapy can reduce chemotherapy-induced peripheral neuropathy in patients with non-metastatic breast cancer receiving taxane-based chemotherapy. The study will also provide information on the feasibility and acceptability of implementing hilotherapy in routine oncology care and explore circulating biomarkers in relation to the development of neuropathy.

• Study Type: Interventional
• Enrollment (Estimated): 148
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Malin Rydholm, MD; Phone Number: +46 31 342 10 00; Email: malin.rydholm@vgregion.se

Study Locations

• Sweden
  • Västra Götaland County
    • Gothenburg, Västra Götaland County, Sweden, 413 45
      • Sahlgrenska University Hospital
      • Contact: Malin Rydholm, MD; Phone Number: +46 31 342 10 00; Email: malin.rydholm@vgregion.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥18 years of age
• Patients with breast cancer scheduled to receive taxane-based chemotherapy in the adjuvant or neoadjuvant setting

Exclusion Criteria:

• Presence of metastatic disease.
• Pre-existing peripheral neuropathy CTCAE grade ≥2.
• Prior treatment with neurotoxic chemotherapy, including taxanes, platinum compounds, vinca alkaloids, or other agents associated with chemotherapy-induced peripheral neuropathy.
• Known cold intolerance or hypersensitivity to cold exposure.
• Contraindications to the use of Hilotherm, including Raynaud's phenomenon or - Raynaud's disease, cryoglobulinemia, severe peripheral arterial disease, cold agglutinin disease, or other clinically significant arterial disorders.
• Insufficient understanding of the Swedish language to complete study procedures and questionnaires.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hilotherapy; Participants receive bilateral hilotherapy of the hands and feet using the Hilotherm® device at a target temperature of 15°C. Cooling is initiated 30 minutes before the chemotherapy infusion, continued throughout the infusion, and maintained for 30 minutes after completion of chemotherapy.	Device: Continuous Controlled Cooling of the Hands and Feet; Bilateral continuous controlled cooling of the hands and feet using the Hilotherm® device at a target temperature of 15°C. Cooling is initiated 30 minutes before the chemotherapy infusion, continued throughout the infusion, and maintained for 30 minutes after completion of the infusion. Cooling is administered at each taxane-based chemotherapy treatment.
No Intervention: Standard Care; Participants receive standard care without a cooling intervention for the prevention of chemotherapy-induced peripheral neuropathy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Clinically Meaningful Chemotherapy-Induced Peripheral Neuropathy	Clinically meaningful chemotherapy-induced peripheral neuropathy (CIPN) is defined as a ≥10-point increase from baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy (EORTC QLQ-CIPN20) sensory subscale score. The EORTC QLQ-CIPN20 is a patient-reported questionnaire assessing symptoms and functional impairment related to CIPN. Scores are transformed to a 0-100 scale, with higher scores indicating greater symptom burden.	From enrollment to 6 months after completion of taxane-based chemotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of NCI-CTCAE Grade ≥2 Peripheral Neuropathy	Incidence of NCI-CTCAE grade ≥2 peripheral sensory neuropathy, peripheral motor neuropathy, and paresthesia. Neuropathy is assessed by healthcare professionals using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 6.0.	Baseline (before chemotherapy), at initiation of taxane treatment (Week 0), at Weeks 3, 6, and 9 (if applicable), and 6 months after completion of taxane treatment.
Change in EORTC QLQ-CIPN20 Motor and autonomic Subscale Score	Change from baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20-item module (EORTC QLQ-CIPN20) motor and autonomic subscale scores. Both subscale scores are transformed to a 0-100 scale (minimum 0, maximum 100). Higher scores indicate greater symptom burden and therefore a worse outcome. Change from baseline reflects the difference between the follow-up and baseline score; accordingly, an increase indicates worsening symptoms, while a decrease indicates improvement.	Baseline (before chemotherapy), at initiation of taxane treatment (Week 0), at Weeks 3, 6, and 9 (if applicable), and 6 months after completion of taxane treatment.
Incremental Cost per Avoided Case of Clinically Meaningful Chemotherapy-Induced Peripheral Neuropathy	Cost-effectiveness will be evaluated as the incremental cost per avoided case of clinically meaningful chemotherapy-induced peripheral neuropathy (CIPN). Direct healthcare costs will include intervention costs, staff time, chemotherapy delivery, and healthcare utilization related to CIPN. Unit of Measure: SEK per avoided case of clinically meaningful CIPN	Through 6 months after completion of chemotherapy
Cost-utility - Incremental Cost per Quality-Adjusted Life Year Gained	Cost-utility will be evaluated as the incremental cost per quality-adjusted life year (QALY) gained. Health utilities will be derived from the EQ-5D and used to estimate QALYs. Incremental costs and incremental QALYs will be compared between the hilotherapy and standard care groups to estimate the incremental cost per QALY gained. Unit of measure: SEK per QALY gained	From baseline through 6 months after completion of taxane-based chemotherapy.
Feasibility and Acceptability of Hilotherapy Implementation	Feasibility and acceptability of implementing hilotherapy in routine oncology care will be assessed through qualitative focus group interviews with nursing staff and management, including experiences and challenges related to implementation.	Prior to intervention start and immediately after completion of the intervention.
Patient Experience of Hilotherapy	Patient experiences of hilotherapy, including perceived benefits, challenges, tolerability, and acceptability, will be assessed through semi-structured individual interviews and analyzed using qualitative content analysis.	From initiation of taxane treatment through completion of taxane treatment, approximately 12 weeks.
Staff Time and Resource Use Associated With Hilotherapy	Difference in time and staff resources between the intervention and control groups. Healthcare personnel will prospectively record time spent on intervention-related activities and additional or unplanned work. Time will be recorded in minutes and aggregated to estimate staff time per patient.	From initiation of taxane treatment through completion of taxane treatment, approximately 12 weeks.
Change in Circulating Neurofilament Light Chain Levels	Circulating neurofilament light chain (NfL) levels will be compared between the hilotherapy and standard care groups over time to evaluate whether hilotherapy influences NfL levels during and after taxane-based chemotherapy. Unit of Measure: pg/mL	NfL assessments: Baseline (before chemotherapy), at initiation of taxane treatment (Week 0), at Weeks 3, 6, and 9 (if applicable; each cycle is 3 weeks), and 6 months after completion of taxane treatment.
Association Between Circulating Neurofilament Light Chain Levels and Subsequent Chemotherapy-Induced Peripheral Neuropathy	Plasma neurofilament light chain (NfL) concentration will be evaluated as a predictor of subsequent clinically meaningful patient-reported chemotherapy-induced peripheral neuropathy (CIPN). Clinically meaningful CIPN will be defined as a ≥10-point increase from baseline in the EORTC QLQ-CIPN20 sensory subscale score. Scores range from 0 to 100, with higher scores indicating greater sensory neuropathy symptom burden. The association will be expressed as the odds ratio for developing clinically meaningful sensory CIPN per 1 standard deviation (SD) increase in NfL concentration. Unit of Measure: Odds ratio per 1 SD increase in NfL concentration	NfL and CIPN assessments: Baseline (before chemotherapy), at initiation of taxane treatment (Week 0), at Weeks 3, 6, and 9 (if applicable; each cycle is 3 weeks), and 6 months after completion of taxane treatment.
Incidence of Adverse Device Effects Related to Hilotherapy	Incidence of adverse device effects related to hilotherapy, including cold intolerance, skin changes, and other adverse events associated with the study device.	From initiation of taxane treatment through completion of taxane treatment, approximately 12 weeks.
Percentage of Participants With Taxane Dose Reduction	Percentage of participants in each treatment group who experience at least one taxane dose reduction during taxane-based chemotherapy.	From initiation of taxane treatment through completion of taxane treatment, approximately 12 weeks.
Impact of Hilotherapy on Chemotherapy Delivery	Comparison between the hilotherapy and standard care groups regarding chemotherapy delivery, including dose reductions, dose delays, and premature treatment discontinuation during taxane-based chemotherapy.	From initiation of taxane treatment through completion of taxane treatment, approximately 12 weeks.
Percentage of Participants With Taxane Dose Delay	Percentage of participants in each treatment group who experience at least one taxane dose delay during taxane-based chemotherapy.	From initiation of taxane treatment through completion of taxane treatment, approximately 12 weeks.
Percentage of Participants With Premature Discontinuation of Taxane Treatment	Percentage of participants in each treatment group who discontinue taxane treatment before completion of the planned treatment course.	From initiation of taxane treatment through completion of taxane treatment, approximately 12 weeks.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association Between Circulating Tau Levels and Subsequent Chemotherapy-Induced Peripheral Neuropathy	Tau concentration will be evaluated as a predictor of subsequent clinically meaningful patient-reported chemotherapy-induced peripheral neuropathy (CIPN). Clinically meaningful CIPN will be defined as a ≥10-point increase from baseline in the EORTC QLQ-CIPN20 sensory subscale score. Scores range from 0 to 100, with higher scores indicating greater sensory neuropathy symptom burden. The association will be expressed as the odds ratio for developing clinically meaningful sensory CIPN per 1 standard deviation (SD) increase in Tau concentration. Unit of measure fot tau: pg/mL Unit of Measure: Odds ratio per 1 SD increase in Tau concentration	Tau and CIPN assessments: Baseline (before chemotherapy), at initiation of taxane treatment (Week 0), at Weeks 3, 6, and 9 (if applicable; each cycle is 3 weeks), and 6 months after completion of taxane treatment.
Circulating Tau Levels During and After Taxane-Based Chemotherapy	Circulating Tau levels will be compared between the hilotherapy and standard care groups over time to evaluate whether hilotherapy influences Big-Tau levels during and after taxane-based chemotherapy. Unit of Measure: pg/mL	Baseline (before chemotherapy), at initiation of taxane treatment (Week 0), at Weeks 3, 6, and 9 (if applicable; each cycle is 3 weeks), and 6 months after completion of taxane treatment.

Collaborators and Investigators

• Sponsor: Vastra Gotaland Region
• Investigators: Principal Investigator: Per Karlsson, MD, PhD, Sahlgrenska University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: September 7, 2026
• First Submitted That Met QC Criteria: October 29, 2026
• First Posted (Actual): November 4, 2026

Study Record Updates

• Last Update Posted (Actual): November 4, 2026
• Last Update Submitted That Met QC Criteria: October 29, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: breast cancer; CIPN; taxanes; cooling; hilotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: 2026-04974-01

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