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

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

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.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Device: Elasto-Gel™; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Anticipated): 51
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dr Kiley Loh Wei-Jen, MD; Phone Number: +65 6436 8000; Email: kiley.loh.w.j@singhealth.com.sg

Study Locations

• Singapore
  • Singapore, Singapore, 169610
    • Recruiting
    • National Cancer Centre Singapore
    • Contact: Dr Kiley Loh Wei-Jen, MD; Phone Number: +65 6436 8000; Email: kiley.loh.w.j@singhealth.com.sg
    • Principal Investigator: Dr Kiley Loh Wei-Jen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of written informed consent prior to any study specific procedures.
2. Age ≥ 21 years old
3. Patients with histologically confirmed early or locally advanced breast cancer
4. Must be receiving 12x weekly sessions of paclitaxel as part of their adjuvant or neo-adjuvant chemotherapy
5. Must have routine chemotherapy lab investigations as per institutional practice
6. Concurrent use of Trastuzumab and/or Pertuzumab for cerbB-2 positive patients as per institutional practice is allowed
7. 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:

1. Patients diagnosed with pre-existing or history of peripheral neuropathy (regardless of cause)
2. Patients with history of Raynaud's disease
3. Prior use of taxane-based chemotherapy
4. Concurrent use of other neuro-toxic chemotherapy with paclitaxel
5. Patients who have had any axillary clearance surgery and without a central venous access device for chemotherapy administration
6. Patients with any severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation in the clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Paclitaxel and Elasto-Gel™ Cryotherapy; 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™; Elasto-Gel™ hypothermia mitts and slippers contain glycerine, which has thermal properties, allowing use for cold therapies.; Drug: Paclitaxel; 80mg/m^2 of Paclitaxel is administered by infusion for 60 mins once a week, for a total of 12 cycles
OTHER: Paclitaxel alone; Paclitaxel will be administered without cryotherapy.	Drug: Paclitaxel; 80mg/m^2 of Paclitaxel is administered by infusion for 60 mins once a week, for a total of 12 cycles

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	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

Collaborators and Investigators

• Sponsor: National Cancer Centre, Singapore
• Collaborators: Singapore General Hospital; Terry Fox Foundation; Duke-NUS Academic Medicine Research Institute
• Investigators: Principal Investigator: Dr Kiley Loh Wei-Jen, MD, National Cancer Centre, Singapore

Publications and helpful links

General Publications

• Ng DQ, Tan CJ, Soh BC, Tan MML, Loh SY, Tan YE, Ong HH, Teng PPC, Chan JJ, Chay WY, Lee J, Lai G, Beh SY, Tan TJY, Yap YS, Lee GE, Wong M, Dent R, Lo YL, Chan A, Loh KW. Impact of Cryotherapy on Sensory, Motor, and Autonomic Neuropathy in Breast Cancer Patients Receiving Paclitaxel: A Randomized, Controlled Trial. Front Neurol. 2020 Dec 18;11:604688. doi: 10.3389/fneur.2020.604688. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2016
• Primary Completion (ANTICIPATED): September 1, 2019
• Study Completion (ANTICIPATED): June 1, 2020

Study Registration Dates

• First Submitted: November 9, 2017
• First Submitted That Met QC Criteria: February 5, 2018
• First Posted (ACTUAL): February 12, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 14, 2018
• Last Update Submitted That Met QC Criteria: March 13, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Neuropathy; Paclitaxel
• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neuromuscular Diseases; Breast Neoplasms; Peripheral Nervous System Diseases; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: 2015/3017

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