Clinical trial NCT06052345: Paclitaxel-induced Polyneuropathy in Breast Cancer: Early Detection, Risk Factors, Quality of Life and Lifestyle Outcomes
Official title: Chemotherapy(paclitaxel)-induced Polyneuropathy in Breast Cancer As Part of the REBECCA Project (REsearch on BrEast Cancer Induced Chronic Conditions Supported by Causal Analysis of Multi-source Data)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Neoplasms
Breast Cancer
Early-stage Breast Cancer
Non-Metastatic Breast Carcinoma
Polyneuropathy Due to Drugs
Polyneuropathy; Drug
Chemotherapy-induced Peripheral Neuropathy
Quality of Life
Keywords: Paclitaxel-induced polyneuropathy
Antineoplastic Agents
Plant Alkaloids
Paclitaxel
Adjuvant Chemotherapy
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
Collaborators: name: Karolinska Institutet
name: Centre for Research and Technology Hellas (CERTH)
First posted: 2023-09-25
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be identified as potential candidates and consecutively recruited from the oncology clinic at Karolinska University Hospital in Solna. Eligible candidates are patients who have been primarily operated for early non-metastatic breast cancer and are recommended by the multidisciplinary conference to receive adjuvant chemotherapy containing paclitaxel.

Brief summary: This is a single center prospective observational cohort study that aims to:

* examine and identify possible risk and susceptibility factors for the incidence and progression of chemotherapy-induced polyneuropathy (CIPN) in female patients primarily operated for early non-metastatic breast cancer who will receive adjuvant chemotherapy containing paclitaxel
* test different neurophysiological methods for early detection of CIPN
* explore changes that underlie the development of CIPN in relation to clinical presentations, neurophysiological assessment, including measures of small nerve fiber dysfunction, and possible biochemical, metabolic and genetic associations
* explore the effects of CIPN in the patient's lifestyle and quality of life for up to 12 months after the initiation of treatment

Detailed description: The patients who follow the inclusion criteria of the study will be asked to complete:

* a baseline evaluation prior to receiving treatment. This will include a bedside clinical-neurological evaluation, nerve conduction studies (NCS) and quantitative sensory tests of thermal threshold (QST), blood sampling, an oral glucose tolerance test, a skin biopsy, and answering of questionnaires for assessment of symptoms of peripheral neuropathy as well as self-reports on their pre-treatment health and lifestyle status and cancer specific symptomatology
* an on-treatment evaluation 4 weeks after the start of the treatment which will include NCS and QST
* a post-treatment evaluation 4 weeks after the end of treatment which will include the evaluations stated above. During this visit the participants will be provided with the REBECCA lifestyle monitoring system which will include a smartwatch, installation of a mobile app and a PC plugin. The patients will be also asked to fill in some self-rated evaluations as in the pre-treatment period. Researchers, based on the outcomes of the participants, will divide them in two study groups A. CIPN-group and B. No CIPN which will be monitored with the REBECCA monitoring system.
* a final evaluation. This will be performed 8 months after the post-treatment evaluation and it will include clinical-neurological evaluation, nerve conduction studies (NCS) and thermal threshold testing (QST). Additionally, the participants will be requested to fill in the same self-rated evaluations as in the baseline and the post-treatment.

Eligibility criteria: Inclusion Criteria:

* Female patients
* Age of ≥ 18 years
* Newly operated primary breast cancer without metastatic disease receiving adjuvant chemotherapy containing paclitaxel
* No prior chemotherapy other than cyclophosphamide and epirubicin
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Written informed consent
* Able to communicate with investigators, participate in testing and comply with the requirements of the study-protocol

Exclusion Criteria:

* Have received drugs suspected/known to cause peripheral neuropathy
* Have history of acquired or inherited neuropathy or other genetic disease with increased tendency to develop neuropathy
* Have known disturbed glucose metabolism, either diabetes mellitus or impaired glucose tolerance
* Have moderate to severe kidney, liver, lung or heart disease
* Have known symptomatic or other advanced spinal stenosis
* Have known autoimmune disease that potentially cause or contribute to neuropathy
* Have known HIV or active HBV or HCV infections
* Have known paraneoplastic syndrome
* Have known alcohol abuse
* Have known pregnancy or nursing

Primary outcomes:
measure: Correlation of significant deterioration in neurophysiological parameters including alterations in morphology of small fibers or reduced IENFD (Intraepidermal Nerve Fiber Density) on first follow up visit and development of CIPN
timeFrame: 1 year
measure: Correlation of abnormal laboratory tests in baseline assessment with development/severity of CIPN
timeFrame: 1 year
measure: Correlation of parameters of NCS, temperature thresholds, and IENFD at baseline screening with development and severity of CIPN
timeFrame: 1 year
measure: Biochemical and metabolic abnormalities prior to paclitaxel treatment and their association with the development of CIPN
timeFrame: 1 year
Secondary outcomes:
measure: Calculate and compare the false negative and false positive rate of CIPN in every used method during follow up
timeFrame: 1 year
measure: Association of altered scoring in different questionnaires (Fact/GOG-Ntx, SFN-SIQ) and different examinations (UENS) with the presence and severity of CIPN
timeFrame: 1 year
measure: Evaluation of whether specific genotypes of breast cancer and higher or lower levels of different proteins are related with higher incidence rate and severity of CIPN
timeFrame: 2 years
measure: Study any correspondence between deterioration of QoL indicated by REBECCA monitoring system and standardized patient self-reported measures with diagnosed CIPN after implementation of different methods during follow up
timeFrame: 2 years
Other outcomes:
Locations:
city: Solna
country: Sweden
facility: Karolinska University Hospital
state: Stockholm
Study officials:
affiliation: Karolinska University Hospital
name: Theodoros Foukakis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: