CIPN-prevention Trial Evaluating the Efficacy of Hand-cooling and Hand-compression (POLAR)

CIPN-prevention Trial Evaluating the Efficacy of Hand-cooling and Hand-compression in Patients Undergoing (Neo-) Adjuvant Chemotherapy for Primary Breast Cancer

The POLAR study is a monocentric, prospective, randomized, 2-arm study designed to evaluate the effectiveness of compression or hypothermia in preventing higher-grade chemotherapy-induced peripheral neuropathy (CIPN) (Grade > 1 according to EORTC) in patients undergoing (neo-)adjuvant chemotherapy with weekly Paclitaxel or Nab-Paclitaxel. In this study, the dominant hand of participants will be either cooled or compressed, while the contralateral hand will serve as a control. The treatment groups will be randomized.

The primary aim of the study is to compare the effectiveness of limb hypothermia versus compression in preventing CIPN. Additionally, the investigators will assess the quality of life and therapy acceptance among the participants in both study arms. Data from the two groups will be collected and compared to determine the most effective intervention for preventing CIPN and to understand the overall impact on patients' well-being and treatment adherence.

Study Overview

• Status: Completed
• Conditions: Chemotherapy-induced Peripheral Neuropathy; Onychodystrophy
• Intervention / Treatment: Device: Limb hypothermia; Device: Limb compression

Detailed Description

This is a prospective, randomized, two-arm study with the aim of assessing the effectiveness of compression or cooling in preventing higher-grade CIPN (>Grade 2 according to EORTC) during weekly paclitaxel or nab-paclitaxel based (neo-)adjuvant chemotherapy. For this purpose, the dominant hand is either cooled or compressed, depending on the study arm, and the contralateral hand is only observed. The allocation to compression or cooling is done through randomization. In a second step, the effectiveness of cooling should be compared with compression. For this purpose, the data collected from the two study arms will be compared. Furthermore, patient satisfaction and quality of life during therapy will be examined. The primary study endpoint is the difference in moderate and severe polyneuropathy (CTCAE grade ≥ 2) compared between the control hand and the intervention hand within the study arms (extremity with cooling vs. control extremity or extremity with compression vs. control extremity). CIPN is evaluated via CTCAE criteria 4.0 and by the Total Neuropathy Score (TNS; clinical version). In addition, sensorimotor symptoms are documented using EORTC QLQ-CIPN20 questionnaires (see also 3.3).

In a second, hierarchical test, the rate of moderate and severe polyneuropathies is compared between the two intervention arms (cooling vs. compression). The rate of onychodystrophies and onycholysis in both intervention arms (compression and cooling) is documented using CTAE criteria and compared between the intervention arm and the control arm as well as between both patient groups.

In addition, patient satisfaction and acceptance of the intervention are examined. EORTC QLQ-C30 questionnaires are used to document quality of life. Any toxicities during therapy are documented according to the CTCAE criteria 4.0.

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Heidelberg, Germany, 69120
    • National Center for Tumor Diseases (NCT)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- all female patients with signed informed consent who are starting with (neo-) adjuvant chemotherapy according to the following protocols:

• 4 x Epirubicin/Cyclophosphamid (EC) q3w, followed by 12 x Paclitaxel weekly or 12x Nab-Paclitaxel (+/- Trastuzumab)
• Paclitaxel or Nab-Paclitaxel weekly without anthracyclines
• Paclitaxel or Nab-Paclitaxel weekly in combination with Carboplatin

Exclusion criteria:

• patients without informed consent
• ECOG-Status > 1
• age under 18 years
• previous chemotherapy
• therapy with SSNRI, SSRI, or tricyclic antidepressants especially duloxetine, gabapentine, pregabaline and amitryptiline.
• known polyneuropathy (e.g. alcoholic PNP, nephrogenic PNP, diabetic PNP etc.)

• Patients having diseases connected to PNP:

  • Sjögren-syndrome, sarkoidosis, amyloidneuropathy, Morbus Fabry, HSAN (Hereditary Sensoric and Autonome Neuropathy)
  • Guillain-Barré-syndrome, acute intermittent porphyria, critical-illness-PNP
  • Vaskulitides, HNPP, diabetic amyotrophy, multifokal motoric neuropathy, Lewis-Sumner-syndrome, borreliosis-neuropathy, Zoster-neuritis, neuralgic shoulder amyotrophy
  • Myelopathy, compression of the myelon, syringomyelia, meningomyelitis, Restless-Legs-syndrome
  • Sulcus-Ulnaris-syndrome, Loge-de-Guyon-syndrome, Medianus-compression-syndrome, multiple sklerosis, AML, Lupus erythematodes, sklerodermia/systemic sclerosis, Ehlers-Danlos-syndrome, CREST-syndrome, Raynaud-syndrome, cold aglutinin disease, hämatologic neoplasms, diabetes mellitus, chronic alcohol abuse, hepatitis C, known severe kidney disease

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: Hypothermia; limb Hypothermia with special hypothermia-gel-gloves of the dominant hand starting 30min before chemotherapy application and ending 30min after. The glove will be changed every 30min to provide constant cooling	Device: Limb hypothermia; Limb hypothermia with special gel-gloves
Experimental: Compression; compression of the dominant hand provided by one-way latex-gloves. The necessary size will be determined after measurement for every Patient individually	Device: Limb compression; compression with sterile one way Latex gloves. Size measured for every Patient individually

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of CIPN grade >1 on the interventional hand compared to the non-interventional hand	Comparing rates of CIPN>grade 1 on the interventional and non-interventional hand by evaluation CTCAE criteria, EORTC QLQ-CIPN-20, the clinical version of the total neuropathy score (TNSc), Magnetic resonance neurography (MRI; n=21) and nerve conduction studies (n=4)	1 year (during taxane therapy and follow up)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of onycholysis/onychodystrophy grade >1 on the interventional hand compared to the non-interventional hand	Comparing rates of onycholysis/onychodystrophy>grade 1 on the interventional and non-interventional hand	1 year (during taxane therapy and follow up)
Magnetic resonance neurography (MRI) as a possible marker of CIPN	To evaluate the role of MRI as a possible marker for CIPN, MRI will be performed in a subset of patient (N=21)	3 month (before and after taxane therapy)
Influence of CIPN on the quality of life	Standardized clinical questionnaires (EORTC QLQ30, QLQ-CIPN-20) are used to determine the quality of life.	1 year (during taxane therapy and follow up)

Collaborators and Investigators

• Sponsor: University Hospital Heidelberg
• Investigators: Study Director: Laura Michel, M.D., University Hospital Heidelberg

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2019
• Primary Completion (Actual): July 15, 2022
• Study Completion (Actual): July 15, 2022

Study Registration Dates

• First Submitted: July 15, 2024
• First Submitted That Met QC Criteria: August 6, 2024
• First Posted (Actual): August 7, 2024

Study Record Updates

• Last Update Posted (Actual): August 7, 2024
• Last Update Submitted That Met QC Criteria: August 6, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Breast cancer; hypothermia; Peripheral neuropathy; CIPN
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases
• Other Study ID Numbers: NCT/HD_GYNONC:POLAR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No