A Novel Limb Cryocompression System for Prevention of Chemotherapy Induced Peripheral Neuropathy

Study Overview
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Brief Summary
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The study aims to investigate the safety and tolerability of limb cryocompression in preventing of Chemotherapy-induced Peripheral Neuropathy via a newly developed limb cryocompression device in healthy subjects and cancer patients. The limb cryocompression device will be tested for its safety in delivering limb cryocompression and efficacy in improving the preservation of peripheral nerves during chemotherapy.

Detailed Description
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The study consists of two parts. The first part of the study will consist of up to 18 healthy subjects to assess safety and tolerability of the new limb cryocompression device. The occurrence or lack of core hypothermia will be studied. The second part of the study will consist of 15 cancer patients recruited from the National University Hospital. Patients will undergo cryocompression over multiple cycles of chemotherapy to establish safety and tolerability of repeated therapy. Cryocompression of the limbs will be administered using cooling wraps attached to a cooling device. The limbs will be cooled from the digits to the elbow/knee.

Official Title
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A Novel Limb Cryocompression System for Prevention of Chemotherapy Induced Peripheral Neuropathy

Conditions
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Chemotherapy-induced Peripheral Neuropathy

Intervention / Treatment
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* Device: Paxman Cryocompression System (PCCS)
* Device: Paxman Cryocompression System (PCCS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For healthy subjects: Age 21-80 years Signed informed consent from patient or legal representative No history of neuropathy ECOG 0 No history of hospitalization in the past 6 months For cancer patients: Age 21- 80 years Signed informed consent from patient or legal representative Scheduled to receive weekly paclitaxel chemotherapy Patients may receive other chemotherapy drugs alongside taxane e.g. Platinum/Herceptin. Exclusion Criteria: For healthy subjects: Open skin wound or ulcers of the limbs History of Raynaud's phenomenon, peripheral vascular disease, or poorly controlled diabetes Pregnant women For cancer patients: Open skin wound or ulcers of the limbs History of Raynaud's phenomenon, peripheral vascular disease, or poorly controlled diabetes Pregnant women

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Healthy subjects will undergo cryocompression of the various temperature and pressure levels in the cryocompression device. One temperature will be tested on 3 subjects for 3 hours. Tolerability of the temperature will be determined through a visual analogue pain scale (VAS). Should 1 out of 3 subjects display intolerance to the temperature level, 3 more healthy subjects will be tested to ensure consistency. Cancer patient limb cryocompression sessions will comprise of a pre-cooling period, continued with paclitaxel infusion and a post-cooling period. Overall, hypothermia will be administered for no longer than four hours. Each patient will undergo maximum limb cooling. The initial device settings for the first cycle for each patient will be based on the optimal temperature determined to be safe and tolerable in healthy subjects. Safety and tolerance of the concomitant cryocompression will be measured using VAS.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy subjects<br>To assess safety and tolerability of limb cryocompression, as well as to determine the optimal temperature and pressure to be used. The occurrence or lack of core hypothermia will be studied. | Device: Paxman Cryocompression System (PCCS)<br>* Establishing optimal temperature and pressure for limb cryocompression therapy. Healthy subjects will undergo 3 hours of limb cryocompression. The cryocompression device used in this study consists of a control unit, and limb wraps. The control unit contains the coolant reservoir and pump to circulate the coolant and air for compression. It is able to thermoregulate (control the temperature of the circulating coolant) and offer cyclic air pressure in the wraps. The wraps cover the limbs from the elbow/knee to the fingers/toes.<br>|
| Experimental: Cancer patients<br>Once the optimal temperature and pressure of limb cryocompression is established in healthy subjects, a group of cancer patients will undergo limb cryocompression over multiple cycles of chemotherapy to establish safety and tolerability of repeated therapy. | Device: Paxman Cryocompression System (PCCS)<br>* The study population will comprise of cancer patients scheduled to receive weekly paclitaxel chemotherapy for a maximum of 12 cycles. Paclitaxel will be administered as a one-hour infusion. Limb cryocompression sessions comprised of a pre-cooling period (up to one hour), continued with paclitaxel infusion and a post-cooling period (on average 30 minutes after the end of paclitaxel infusion). Overall, limb cryocompression will be administered for no longer than four hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events in healthy volunteers, over the duration of a limb cryocompression cycle, as assessed by Common Terminology Criteria for Adverse Events 5.0 | Defined as the number of subjects with treatment-related adverse events as assessed by CTCAE v5.0. Grade 1-5 refer to the severity of the adverse event with higher grade indicating greater severity. Grade 3 and above will be considered severe. | During limb cryocompression procedure, 3 hours for healthy subject | 
| Difference in tolerance scores in healthy volunteers, over the duration of a limb cryocompression cycle, as assessed by Visual Analogue Scale for pain | Defined as the number of subjects with treatment-related intolerance as assessed by tolerability scale, visual analog scale (VAS). On a scale of 0 to 10, a higher VAS score indicates higher intolerance. A score of 8 out of 10 will be considered dose-limiting intolerance. | During limb cryocompression procedure, 3 hours for healthy subject | 
| Incidence of Treatment-Emergent Adverse Events in cancer patients, over the duration of a limb cryocompression cycle, as assessed by Common Terminology Criteria for Adverse Events 5.0 | Defined as the number of patients with treatment-related intolerance as assessed by CTCAE v5.0. Grade 1-5 refer to the severity of the adverse event with higher grade indicating greater severity. Grade 3 and above will be considered severe. | During every cycle of paclitaxel chemotherapy (each cycle is 1 week) along with cryocompression which may last up to 4 hours, and for up to 12 cycles of weekly Paclitaxel treatment | 
| Difference in tolerance scores in cancer patients, over the duration of a limb cryocompression cycle, as assessed by Visual Analogue Scale for pain | Defined as the number of patients with treatment-related intolerance as assessed by tolerability scale, visual analog scale (VAS). On a scale of 0 to 10, a higher VAS score indicates higher intolerance. A score of 8 out of 10 will be considered dose-limiting intolerance. | During every cycle of paclitaxel chemotherapy (each cycle is 1 week) along with cryocompression which may last up to 4 hours, and for up to 12 cycles of weekly Paclitaxel treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in tolerance scores between various temperature and pressure using Common Terminology Criteria for Adverse Events 4.0 and Visual Analogue Scale for pain | Difference in tolerance scores between various temperature and pressure as assessed by CTCAE v4.0 and tolerability scale, visual analog scale (VAS). On a scale of 0 to 10, a higher VAS score indicates higher intolerance. A score of 8 out of 10 will be considered dose-limiting intolerance. | During limb cryocompression procedure, 3 hours for healthy subject | 
| Difference in qualitative symptom scores using the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale | Difference in qualitative symptom scores using the EORTC QLQ-CIPN-20 scale before, at the end of paclitaxel chemotherapy with limb cryocompression, and at 3,6 and 12 months post-treatment. | Before start of weekly paclitaxel chemotherapy, at the end of 12 cycles of weekly paclitaxel treatment, at 3-, 6-, and 12-months post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chemotherapy-induced Peripheral Neuropathy, Cryocompression