Clinical trial NCT06541769: CIPN-prevention Trial Evaluating the Efficacy of Hand-cooling and Hand-compression
Official title: CIPN-prevention Trial Evaluating the Efficacy of Hand-cooling and Hand-compression in Patients Undergoing (Neo-) Adjuvant Chemotherapy for Primary Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chemotherapy-induced Peripheral Neuropathy
Onychodystrophy
Keywords: Breast cancer
CIPN
Peripheral neuropathy
hypothermia
Lead sponsor: University Hospital Heidelberg
Sponsor class: OTHER
First posted: 2024-08-07
Enrollment: 122
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of CIPN grade >1 on the interventional hand compared to the non-interventional hand
timeFrame: 1 year (during taxane therapy and follow up)
Secondary outcomes:
measure: Incidence of onycholysis/onychodystrophy grade >1 on the interventional hand compared to the non-interventional hand
timeFrame: 1 year (during taxane therapy and follow up)
measure: Magnetic resonance neurography (MRI) as a possible marker of CIPN
timeFrame: 3 month (before and after taxane therapy)
measure: Influence of CIPN on the quality of life
timeFrame: 1 year (during taxane therapy and follow up)
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: National Center for Tumor diseases (NCT)
Study officials:
affiliation: University Hospital Heidelberg
name: Laura Michel, M.D.
role: STUDY_DIRECTOR
References: