Clinical trial NCT06449417: Aurora: a Human-centered Program for Breast Cancer Patients in Chile, Easing Neoadjuvant Chemotherapy's Effects
Official title: Aurora's Impact on Mitigating Adverse Effects of Neoadjuvant Chemotherapy in Breast Cancer Patients in Chile's Metropolitan Region.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: Physical Activity
Quality of Life
Fatty Acids
Lead sponsor: Pontificia Universidad Catolica de Chile
Sponsor class: OTHER
First posted: 2024-06-10
Enrollment: 30
Sex: FEMALE
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a mixed-methods Randomized Control Trial evaluating the impact of Aurora, a human-centered design, on breast cancer patients undergoing neoadjuvant chemotherapy in the Metropolitan Region of Chile. The study measures quantitative and qualitative variables over a 9-week intervention. The control group comprises patients without Aurora. The primary outcome is quality of life, with secondary outcomes including functional capacity and tumor progression. The study includes sociodemographic data extraction, baseline and intervention end measurements, and correlations between variables. The Aurora program integrates motivation, peer learning, and community support. The hypothesis is that Aurora enhances the biopsychosocial effects and mitigates adverse physical and biological consequences of breast cancer by promoting physical activity.
Primary purpose: PREVENTION

Brief summary: Breast cancer is the most prevalent cancer worldwide and the leading cause of cancer death among women in Chile. The Aurora intervention program is designed to improve the quality of life and mitigate the physical consequences of breast cancer in patients undergoing neoadjuvant chemotherapy. It aims to promote physical activity through a human-centered design product system, incorporating elements of personal motivation, peer learning, and community engagement in alignment with the COM-B model.

In a 9-week randomized controlled trial, we will include 30 female patients under 70 years undergoing neoadjuvant therapy for breast cancer in the Metropolitan Region of Chile. Baseline and post-intervention measurements will assess biopsychosocial breast cancer effects through a questionnaire as well as adverse physical effects through functional capacity tests. Biological consequences will be evaluated through lipid profiling, inflammation biomarkers, and tumor progression. In addition, Aurora's patient perception of behavior change will be addressed by analyzing the patient's records in a journal. Moreover, the perceived value of Aurora's design attributes influencing behavior change will be studied through in-depth interviews.

Preliminary results describe Aurora's design process and indicate that it is well-received by patients, especially as its logbook is a valuable tool for self-reflection and progress tracking. The study anticipates the confirmation that significantly higher physical activity, improved quality of life, and enhanced functional capacity will be attained in the intervention group.

The Aurora intervention program represents a novel approach to support breast cancer patients undergoing chemotherapy, emphasizing physical activity, peer learning, and self-reflection. The integration of the behavior change COM-B model and a human-centered design provides a facilitating tool for tailored interventions for breast cancer patients' needs. Yet, the potential correlation between physical activity, fatty acid metabolism, and chemotherapy response necessitates further exploration.

The Aurora intervention program shows promise as a supportive tool for breast cancer patients undergoing neoadjuvant chemotherapy. Further research is imperative to evaluate the intervention's impact on patient outcomes, refine the design based on user feedback, and explore potential relationships among physical activity, fatty acid metabolism, and chemotherapy response.

Detailed description: The research question of this project focuses on the quantitative and qualitative dimensions in health concerning temporality, specifically exploring and understanding health phenomena in a specific temporal context within the framework of the intervention with the Aurora human centered design product system therapeutic intervention program. The hypothesis is that the Aurora program significantly enhances the biopsychosocial breast cancer effects and mitigates breast cancer's adverse physical and biological consequences among women undergoing neoadjuvant chemotherapy in the Metropolitan Region of Chile by promoting physical activity. The main goal is to evaluate the impact of the Aurora product system therapeutic intervention program on enhancing the biopsychosocial effects and mitigating the adverse physical and biological consequences of breast cancer for women undergoing neoadjuvant chemotherapy in the Metropolitan Region of Chile by promoting physical activity.The specific objectives are:

i) Evaluate the impact of the Aurora human centered design product system therapeutic intervention program on Physical Activity levels (measured by intensity, time, and adherence) among women undergoing neoadjuvant chemotherapy in the Metropolitan Region of Chile by comparing the intervention and control groups at baseline and at the end of the program.

ii) Assess the effectiveness of the Aurora human centered design product system therapeutic intervention program in enhancing the biopsychosocial effects of breast cancer (measured by quality of life and patient´s perceptions) among women undergoing neoadjuvant chemotherapy in the Metropolitan Region of Chile by comparing the intervention and control groups at baseline and at the end of the program.

iii) Determine the extent to which the Aurora human centered design product system therapeutic intervention program mitigates the physical consequences of breast cancer (measured by functional capacity) among women undergoing neoadjuvant chemotherapy in the Metropolitan Region of Chile by comparing the intervention and control groups at baseline and at the end of the program.

iv) Examine the role of the Aurora human centered design product system therapeutic intervention program in reducing the biological consequences of breast cancer (measured by lipid profile LDL, HDL, and RBCm FA; inflammation by CRP and neutrophil to lymphocyte ratio; and tumor progression by residual cancer burden and pathological complete response) among women undergoing neoadjuvant chemotherapy in the Metropolitan Region of Chile by comparing the intervention and control groups at baseline and at the end of the program.The study program consists of four main phases: Week 0-4: Patients provide informed consent, and sociodemographic data, breast cancer subtype, and stages are collected. An online educational session is held, detailing physical activity advantages and outlining recommended exercise types, durations, and frequencies for breast cancer patients. Participants' availability is gathered to schedule an online assessment, which includes the quality of life questionnaire, functional capacity evaluations, and a dietary survey. Blood samples are drawn from routine tests in coordination with their neoadjuvant chemotherapy indication or schedule.

Week 4-13: Participants are randomized using minimization, considering each new participant's characteristics, such as age and cancer stage, which are determinant factors for physical activity adherence. Participants receive kits tailored to their assigned group, complete with instructions on using each item and what to document in the provided journal over the nine-week intervention period. Participants in the intervention group receive the Aurora human centered design product system, while those in the control group receive a kit with the same hydration bottle, measurement tape, a logbook journal with blank pages, and an electronic step count wristband, all packaged in an Aurora-branded tote bag. Weekly follow-ups ensure compliance with the protocol and record any adverse events.

Week 13-16: The research team coordinates the return of the kits. Participants in the intervention group return the container with all the sports equipment and the dedication letter to the next participant. The team confirms whether the participant wishes to keep the journal, and if so, each page is photographed for record-keeping before returning it to the participant. The participant also keeps the water bottle. In the control group, the same procedure is followed for the journal delivery, and participants keep the tote bag and the water bottle. They return the measurement tape and the pedometer. Prior to surgery, each patient undergoes routine blood sampling for testing, following the same procedure as at baseline.The experimental procedures involve determining physical activity levels, physical activity adherence, quality of life, and Aurora's perception. Physical activity levels are measured according to the number of exercise sessions reported on a weekly basis and their compliance with the reported minimum of 3 weekly sessions for breast cancer patients in Chile. The intervention group receives specially designed pages in their Aurora journal to register this information, whereas the control group has blank pages to record the data. Physical activity time is evaluated at baseline and at the end of the intervention with the International Physical Activity questionnaire in its short form. Physical activity intensity is measured using wrist pedometers provided by the Oncology physical therapy unit at Complejo Asistencial Dr. Sótero del Río. Quality of Life is assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23 questionnaire at baseline and at the end of the intervention. To understand Aurora's perception, two methods are assessed at the end of the intervention: a thematic analysis of the Aurora journals and a system design evaluation. The reflections recorded in the Aurora logbook journal are transcribed and analyzed using an inductive thematic analysis following the COM-B constructs. The system design evaluation is conducted in online, in-depth, focused interview sessions with participants from the intervention group at the end of the last patient's cycle.

The method for extracting and measuring fatty acids (FA) involves drawing 5 ml of venous blood after a 12-hour fast, separating red blood cells, and extracting plasma membranes following a specific procedure. The FA from these membranes are then extracted using the Folch method, which uses a mixture of chloroform and methanol to extract lipids. The FA are derivatized to form fatty acid methyl esters (FAMEs) for analysis by gas chromatography to determine the fatty acid composition. Neutrophil and lymphocyte counts ratio (NLR) will be obtained from a complete blood count, and omega-3 (⍵-3) and omega-6 (⍵-6) PUFAs will be determined by extracting total lipids from red blood cells and total plasma. Residual cancer burden (RCB) and pathological complete response (pCR) will be calculated post-surgery based on data from electronic medical records to assess tumor progression.

The statistical analysis will be performed using R Studio, and the results will be analyzed under the intention-to-treat principle. Descriptive, inferential, and correlation analyses will be conducted, with statistical significance defined as p≤0.05. Descriptive statistics will present the results as the mean and standard deviation for continuous variables with a symmetrical distribution or as percentiles and range for continuous variables with an asymmetrical distribution. Inferential statistics will compare baseline characteristics and within-group and between-group differences using t-tests, Pearson´s chi-square tests, or non-parametric tests, respectively, for data distribution.

Eligibility criteria: Inclusion Criteria:

* Women under 70 years old
* Diagnosis of primary breast carcinoma,
* Indication for neoadjuvant chemotherapy
* Access to a safe physical space for performing PA
* Connection to the Internet
* Access to an electronic device for video conferencing

Exclusion Criteria:

* Stage IV cancer (non-curative)
* Medical contraindication to physical activity
* Self-report of physical activity participation equivalent to the current governmental physical exercise recommendation guide
* Body mass index lower than 18.5 kg/m2 or greater than 40 kg/m2.

Primary outcomes:
measure: Quality of Life Perception Score
timeFrame: 9 weeks
Secondary outcomes:
measure: Patient Perception
timeFrame: 9 weeks
measure: Lipid Profile
timeFrame: 9 weeks
measure: Change on aerobic capacity measured with the Two-Minute Walk Test at baseline and at the end of the program.
timeFrame: 9 weeks
measure: Change in arm volume measured with the 6 Measures Assessment of Arm Volume at baseline and at the end of the program.
timeFrame: 9 weeks
measure: Change in upper extremity strength measured with the 30-second elbow extension test at baseline and at the end of the program.
timeFrame: 9 weeks
measure: Change in lower extremity strength measured with the 30 Seconds Sit-to-Stand Test, at baseline and at the end of the program.
timeFrame: 9 weeks
measure: Change in C-reactive protein measured in blood samples, at baseline and at the end of the program.
timeFrame: 9 weeks
measure: Change in Neutrophil-to-Lymphocyte Ratio in blood samples, at baseline and at the end of the program.
timeFrame: 8 months
measure: Residual cancer burden score after neoadjuvant treatment.
timeFrame: 8 months
measure: Pathological complete response measured after neoadjuvant chemotherapy
timeFrame: 8 months
measure: Change in lipid profile measured by Low Density Lipoprotein on blood sample, at baseline and at the end of the program.
timeFrame: 9 weeks
measure: Change in lipid profile measured by High Density Lipoprotein on blood sample, at baseline and at the end of the program.
timeFrame: 9 weeks
measure: Change in lipid profile measured by Red Blood Cell membrane Fatty Acid w3 on blood sample, at baseline and at the end of the program.
timeFrame: 9 weeks
measure: Change in lipid profile measured by Red Blood Cell membrane Fatty Acid w6 on blood sample, at baseline and at the end of the program.
timeFrame: 9 weeks
measure: Change in lipid profile measured by the 24-hour dietary recall questionnaire, at baseline and at the end of the program.
timeFrame: 9 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Pontifica Universidad católica de Chile
name: Viviana Montecinos, Professor
role: STUDY_DIRECTOR
References:
citation: Ramirez K, Acevedo F, Herrera ME, Ibanez C, Sanchez C. [Physical activity and breast cancer]. Rev Med Chil. 2017 Jan;145(1):75-84. doi: 10.4067/S0034-98872017000100011. Spanish.
citation: Acevedo F, Walbaum B, Medina L, Merino T, Camus M, Puschel K, Ramirez K, Manzor M, Veglia P, Martinez R, Guerra C, Navarro M, Bauerle C, Dominguez F, Sanchez C. Clinical characteristics, risk factors, and outcomes in Chilean triple negative breast cancer patients: a real-world study. Breast Cancer Res Treat. 2023 Jan;197(2):449-459. doi: 10.1007/s10549-022-06814-x. Epub 2022 Nov 21.
citation: Valenzuela R, Walbaum B, Farias C, Acevedo F, Vargas C, Bennett JT, Bravo ML, Pinto MP, Medina L, Merino T, Ibanez C, Parada A, Sanchez C. High linoleic acid levels in red blood cells predict a poor response to neoadjuvant chemotherapy in human epidermal growth factor receptor type 2-positive breast cancer patients. Nutrition. 2024 May;121:112357. doi: 10.1016/j.nut.2024.112357. Epub 2024 Jan 9.