Clinical trial NCT06400849: Comparison of the Efficacy of Cryotherapy Combined With Compression in Preventing Neuropathy
Official title: Comparison of the Efficacy of Cryotherapy Combined With Compression in Preventing the Development of Paclitaxel-induced Peripheral Neuropathy in Non-metastatic Breast Cancer: A Prospective, Single-centre, Self-controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Non-metastatic Breast Cancer
Keywords: Non-metastatic breast cancer
Peripheral neuropathy
paclitaxel
cryotherapy
compression therapy
Lead sponsor: Centre Antoine Lacassagne
Sponsor class: OTHER
Collaborators: name: Thuasne
First posted: 2024-05-06
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, single-centre, randomised (1:1), stratified, self-controlled cohort study
Primary purpose: PREVENTION

Brief summary: Breast cancer is the most frequently diagnosed cancer in the world. In France, 58,000 new cases were detected in 2018. Breast cancer is therefore the most common cancer in women. The 5-year survival rate for all stages combined is 88%. These excellent survival figures have been achieved thanks to improvements in treatment, including the advent of chemotherapy. The majority of patients will be cured of their cancer, so post-cancer quality of life is a major issue, hence the importance of trying to reduce long-term sequelae.

Taxanes are one of the main cytotoxic anticancer agents used in the treatment of breast cancer. However, taxanes have a direct effect on the central and peripheral nervous systems and can induce chemotherapy-induced peripheral neuropathy (CIPN). The mechanisms of NPIC by taxanes are not fully understood. CINP is manifested by symptoms of paresthesia, numbness, burning, pain, altered temperature perception, myalgia, myopathy, fine motor difficulties, gait and balance disturbances, muscle weakness in the lower limbs and/or functional decline.

NPIC occurs in 80 to 97% of patients treated with taxanes and is the main limiting toxicity during paclitaxel administration. NPIC often leads to postponement or reduction of dose, or even discontinuation of treatment. In addition, NPIC may last for several months or even years after the end of anti-cancer chemotherapy and represents the main long-term sequelae. This can promote and/or exacerbate symptoms of psychological distress (depressive symptoms and symptoms of anxiety) and lead to a reduction in quality of life (QoL). Prevention of NIPC is therefore a major issue in breast cancer treatment. According to the 2014 guidelines from the American Society of Clinical Oncology, prevention and treatment of IPN are inadequate with current weapons, and there is an urgent need to evaluate and find new methods of prevention. One of the challenges in the management of NIPC will be to reduce the pain induced without diminishing the anti-tumour effect of anti-cancer agents.

In recent years, the effectiveness of cryotherapy using a frozen glove and compression therapy using surgical gloves (SG) in preventing taxane-induced PINC has been reported. During chemotherapy, patients wore a frozen glove on one hand and two surgical gloves of the same size on the other hand continuously. Recent study explained how compression therapy and cryotherapy shared a similar mechanism of reducing drug exposure due to vasoconstriction during paclitaxel infusion. The low temperature associated with cryotherapy would reduce paclitaxel uptake and peripheral nerve damage, or mechanotransduction, and allow a reduction in NIPC.

To date, no study has investigated the efficacy of combining the two means of prevention. The current standard at the Centre Antoine Lacassagne is cryotherapy. The aim of this prospective, self-controlled trial is therefore to compare the efficacy of cryotherapy combined with compression prevention versus cryotherapy alone in preventing paclitaxel-induced peripheral neuropathy in patients undergoing adjuvant treatment for localised breast cancer.


Eligibility criteria: Inclusion Criteria:

* Patient age ≥ 18 years ;
* Performance Status (PS): 0 to 2
* Women with localised or locally advanced breast cancer of any histology
* Indication for treatment with 3 to 4 cycles of paclitaxel (+/- trastuzumab, pertuzumab, carboplatin or endoxan) as adjuvant or neoadjuvant therapy. The choice of the number of cycles will be at the investigator's discretion.
* Symmetry of upper limb peripheral neuropathy grade ≤ 1 according to CTCAE version 5.0 at inclusion.
* Presence of radial pulses in the upper limbs.
* Presence of tibio-posterior and tibio-anterior ankle pulses or ankle systolic pressure index \> 0.9.
* Patient has read the information note and signed the informed consent form.
* The patient is covered by social security.

Exclusion Criteria:

* Patient age \< 18 years
* Patients diagnosed with metastatic or bilateral breast cancer
* Patients with metastatic disease of any location
* Peripheral neuropathy grade ≥ 2 according to CTCAE version 5.0 of the upper or lower limbs
* Patients with asymmetric upper limb peripheral neuropathy grade \> 1 according to CTCAE version 5.0 at inclusion.

  \*In the case of asymmetry of the lower limbs of grade \> 1 according to CTCAE version 5.0, the patient will not be considered a failure in selection but the corresponding secondary criteria will not be analysed.
* Patients with underlying medical conditions that could potentially cause peripheral neuropathy (diabetes mellitus, chronic alcoholism, unilateral lymphoedema or postherpetic neuralgia), or any other reason based on the investigator's judgement.
* Diagnosed Raynaud's syndrome
* Obstructive arterial disease of the lower limbs
* History of myocardial infarction
* Patients already using compression foot socks
* Vulnerable populations and participants defined in Articles 64 to 68 of Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017:

  * Pregnant women
  * Incapacitated participants who have not given their free and informed consent or refused to do so before the onset of their incapacity, who do not fall under the provisions of Article 64 ;
  * Pregnant or breast-feeding women who are not covered by the provisions of article 66;
  * Persons of full age who are the subject of a legal protection measure or who are unable to express their consent.

Primary outcomes:
measure: To compare the efficacy in preventing peripheral neuropathy as determined by medical staff between cryotherapy treatment alone and combined cryotherapy and compression treatment of the upper limbs in patients treated with paclitaxel.
timeFrame: 7 days after completion of C3D15 or C4D1 if applicable (each cycle is 21 days)
Secondary outcomes:
measure: To compare the efficacy of cryotherapy alone and combined cryotherapy and compression treatment of the upper limbs in reducing the occurrence of peripheral neuropathy as determined by medical staff throughout the course of treatment.
timeFrame: At inclusion, just before each treatment cycle (C1D1, C2D1, C3D1) (each cycle is 21 days), at 1 month (±2 weeks) and at 4 months after the end of chemotherapy (±2 weeks)
measure: To compare the efficacy of cryotherapy alone and combined cryotherapy and compression treatment of the lower limbs in reducing the occurrence of peripheral neuropathy as determined by medical staff throughout the course of treatment.
timeFrame: At inclusion, just before each treatment cycle (C1D1, C2D1, C3D1 and 7 days after C3D15 or C4D1 if applicable), (each cycle is 21 days) at 1 month (±2 weeks) and at 4 months after the end of chemotherapy (±2 weeks)
measure: To compare the efficacy of cryotherapy alone and combined cryotherapy and compression treatment of the lower limbs in reducing the occurrence of peripheral neuropathy as determined by the patient throughout the course of treatment.
timeFrame: At inclusion, just before each treatment cycle (C1D1, C2D1, C3D1 and 7 days after C3D15 or C4D1 if applicable) (each cycle is 21 days), at 1 month (±2 weeks) and at 4 months after the end of chemotherapy (±2 weeks)
measure: Comparing cryotherapy tolerance rates with and without compression
timeFrame: During D1, D8 and D15 of all cycles ((each cycle is 21 days)
measure: Evaluate the impact of compression on the temperature at the extremities
timeFrame: 15 minutes before and after removal of cryotherapy and compression devices at D1, D8 and D15 of each chemotherapy cycle (each cycle is 21 days)
measure: Study the percentage and characteristics of peripheral neuropathy according to the DN4 questionnaire during treatment
timeFrame: C1D1, C2D1, C3D1 and 7 days after C3D15), (each cycle is 21 days) at 1 month (±2 weeks) and 4 months after the end of chemotherapy (±2 weeks).
Other outcomes:
Locations:
city: Nice
country: France
facility: Centre Antoine Lacassagne
Study officials:
References: