Regional Cryotherapy in Preventing Paclitaxel Induced Peripheral Neuropathy in Breast Cancer Patients

Study Overview
=================
Brief Summary
-----------------
The trial will be preceded by a pilot phase study in 5 patients. This will then be followed by the randomized 1:1 phase II trial testing the utility of regional cryotherapy in preventing or reducing paclitaxel-induced peripheral neuropathy compared to no treatment. It is hypothesized that cryotherapy causes regional blood vessel constriction and decreases the paclitaxel exposure to the distal epithelial nerve fibres, thus resulting in decreased nerve damage.

Official Title
-----------------
Regional Cryotherapy in Preventing Paclitaxel Induced Peripheral Neuropathy in Patients With Early and Locally Advanced Breast Cancer

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Device: Elasto-Gel™
* Drug: Paclitaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of written informed consent prior to any study specific procedures. Age ≥ 21 years old Patients with histologically confirmed early or locally advanced breast cancer Must be receiving 12x weekly sessions of paclitaxel as part of their adjuvant or neo-adjuvant chemotherapy Must have routine chemotherapy lab investigations as per institutional practice Concurrent use of Trastuzumab and/or Pertuzumab for cerbB-2 positive patients as per institutional practice is allowed Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations. Exclusion Criteria: Patients diagnosed with pre-existing or history of peripheral neuropathy (regardless of cause) Patients with history of Raynaud's disease Prior use of taxane-based chemotherapy Concurrent use of other neuro-toxic chemotherapy with paclitaxel Patients who have had any axillary clearance surgery and without a central venous access device for chemotherapy administration Patients with any severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation in the clinical study.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paclitaxel and Elasto-Gel™ Cryotherapy<br>Cryotherapy will be applied using Elasto-Gel™ hypothermia mitts and slippers for 15 minutes before, during and 15 minutes after each paclitaxel infusion. | Device: Elasto-Gel™<br>* Elasto-Gel™ hypothermia mitts and slippers contain glycerine, which has thermal properties, allowing use for cold therapies.<br>Drug: Paclitaxel<br>* 80mg/m^2 of Paclitaxel is administered by infusion for 60 mins once a week, for a total of 12 cycles<br>|
| Other: Paclitaxel alone<br>Paclitaxel will be administered without cryotherapy. | Drug: Paclitaxel<br>* 80mg/m^2 of Paclitaxel is administered by infusion for 60 mins once a week, for a total of 12 cycles<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients reporting level C and above subjective symptoms, in cryotherapy arm versus controlled arm, based on the Patient Neurotoxicity Questionnaire (PNQ) at 3 months after baseline | PNQ scale ranges from scores A to E; with scoring of A being not affected neuropathy, and E with the worst neuropathy | From commencement to completion of 12 paclitaxel infusions - estimated 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients reporting level C and above subjective symptoms, in cryotherapy arm versus controlled arm, based on the Patient Neurotoxicity Questionnaire (PNQ) at 15 months after baseline |  | From commencement to completion of primary chemotherapy - estimated 15 months | 
| Proportion of patients with lower sensory velocity and amplitudes (based on nerve conduction tests), in cryotherapy arm versus controlled arm, at 15 months after baseline |  | From commencement to completion of primary chemotherapy - estimated 15 months | 
| Incidence of adverse events, in cryotherapy arm versus controlled arm |  | From commencement to completion of 12 paclitaxel infusions - estimated 3 months | 
| Proportion of patients reported intolerance and require cessation of therapies, in cryotherapy arm versus controlled arm |  | From commencement to completion of 12 paclitaxel infusions - estimated 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Paclitaxel, Neuropathy