Clinical trial NCT05297773: Resistance vs. Aerobic Training on Breast Cancer Patients Undergoing Neoadjuvant Treatment
Official title: Effects of Resistance vs. Aerobic Training on Ki-67 and Other Health-Related Biomarkers: The NEO-Program, a Randomized Controlled Trial on Breast Cancer Patients Undergoing Neoadjuvant Treatment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: Exercise
Quality of life
Neoadjuvant treatment
Tumor biology
Physical fitness
Sleep quality
Lead sponsor: Fundacao Champalimaud
Sponsor class: OTHER
Collaborators: name: Faculdade de Motricidade Humana - Universidade de Lisboa
First posted: 2022-03-28
Enrollment: 132
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be followed in a randomized controlled trial conducted during the full duration of neoadjuvant treatment (i.e. 4- to 6-months, depending on patient treatment plan) and two cohorts will be defined: A - breast cancer patients undergoing chemotherapy; B - breast cancer patients undergoing endocrine therapy. Within each cohort, the participants will be divided into three groups: 1) aerobic training; 2): resistance training; 3): control group.

The intervention is designed to have equal energy expenditure throughout the exercise sessions in both exercise groups (10 kcal/kg/week). All training groups will complete 3 sessions/week. To ensure that both exercise groups are isoenergetic, a portable gas analyzer will be used and blood lactate will be collected.

Mandatory thematic sessions about several topics such as physical activity guidelines, active lifestyle will be implemented.
Primary purpose: SUPPORTIVE_CARE

Brief summary: A recent consensus study suggested that understanding the impact of exercise on the tumor microenvironment and therapy effectiveness is paramount and should be considered as a research priority. Therefore, the research team intends to address some of the scientific challenges proposed, which represent clear gaps in the current knowledge.

The investigators propose a randomized controlled trial conducted during all neoadjuvant treatment duration that aims to evaluate and compare the effects of two different exercise protocols (aerobic and resistance training) against a relaxation control group on Ki-67% changes as the main outcome in breast cancer patients. Secondary outcomes will be body composition; resting metabolic rate; physical fitness; quality of life, fatigue, depression/anxiety; accelerometry data (physical activity levels, sedentary time); sleep quality; tumor biology (size, hypoxia, and immune profile); glycemic, lipid, and inflammatory profile.

This project will help not only researchers with the design of future exercise intervention protocols but will also help exercise physiologists in the decision-making process when defining training programs. Moreover, the investigators expect that this research program will encourage more cancer patients to exercise. The team expects that patients with breast cancer engaging in structured exercise will show a more marked decrease in Ki-67, tumor size, and hypoxia and increase the tumor-infiltrating lymphocytes (TILs) compared to controls. The investigators anticipate a more noticeable decrease in the preoperative endocrine prognostic index (PEPI) score and in the Residual Breast Cancer (RCB) in both training groups (respectively with hormonal and chemotherapy). Also, frequent declines in physical fitness are expected to be mitigated in exercisers. It is hypothesize that aerobic training will ameliorate cardiorespiratory fitness and fat mass, while the effects of resistance training will be more relevant for muscle strength, muscle mass, and bone health. Both exercise groups will show greater improvements in quality of life, fatigue, depression, anxiety, and sleep quality. Regarding glycemic, lipid, and inflammatory profiles, the investigators expect to see more favorable changes in both training groups, with a more evident decrease in fasting glucose and insulin, HbA1c%, total and LDL-cholesterol, and triglycerides, and the increase in HDL-cholesterol. The increase in C-reactive protein (CRP), tumor necrosis factor -α (TNF-α), interleukin-6 (IL-6), IL-8, IL-1β, IL-1ra, and insulin-like growth factor-1 (IGF-1) and the decrease in brain-derived neutrotophic factor (BDNF), IL-12p70, IL-10, oncostatin M will be smaller in exercise groups.

Detailed description: Exercise plays a crucial role in breast cancer prevention and more recently it appears as a safe, non-pharmacological, and cost-effective adjuvant therapy for cancer. Indeed exercise improves the quality of life, fatigue, physical fitness, and also has a positive impact on tumor intrinsic characteristics.

Most of the studies regarding the effects of exercise in breast cancer patients were performed after surgery or in survivors. Despite being a window of opportunity to study the impact of exercise on biological properties of the tumor, namely on proliferation markers, the investigations conducted during the neoadjuvant period are still scarce and most of the literature derives from animal studies. Although originating from pilot investigations, the initial human-based evidence suggests that exercise interventions are feasible during neoadjuvant therapy and can potentially reduce some proliferation markers such as Ki-67 (i.e. a widely used prognostic marker), induce favorable changes in tumor-related genes, and increase survival.

Power and sample calculations (G-Power, Version 3.1.9.2) are based on an effect size of 0.25 for KI-67 while using ANOVA - repeated measures within-between interactions, a power of 0.80, a significance of 0.05, and an expected dropout of 40%. The calculation yielded a total sample size of 120 participants (60 undergoing chemotherapy and 60 undergoing hormone therapy: 20 participants per group per each treatment). The power and sample calculations were performed using a study that reported the effect of medication on KI-67 since no study has evaluated the effects of an exercise intervention on that variable and has obtained significant results.

Participants will be recruited to take part in an intervention study for breast cancer patients undergoing neoadjuvant treatment. The recruitment will take place at Champalimaud Clinical Center Breast Unit / Champalimaud Foundation.

To improve exercise adherence, the following strategies will be implemented:

* Thematic sessions about several topics such as physical activity (PA) guidelines, active lifestyle, nutrition, the benefits of exercise for breast cancer patients, etc. Each session will last 1-hour (30 minutes presentation + 30 minutes discussion/questions) and will occur once a month. These thematic sessions are mandatory.
* Group activities: once a month, a group activity will be promoted (exercise outdoor sessions, group walk, group dinner, etc.). In these group activities, participants may invite family members to participate.
* The NEO-program website presenting the mission/goals, team members, activities, news and events, contacts, etc.
* Facebook and Instagram account (share information and photos); before the intervention, written consent for image collection will be requested.

The investigator records clinical data, using a paper or electronic case report form (CRF), all data is collected in an online database that is available through the Champalimaud Clinical Center intranet. Participating physicians have a personal account to log in to the registration page and access the electronic CRF. They will have permanent access to their series of patients.

The participating physician ensures the confidentiality, accuracy, completeness, legibility, and timeliness of the data recorded. Data handling and statistical analysis will be done anonymously by the investigator, with the subject identification code list only available to the local investigator (and research nurse if applicable) working in the local center. The code will be based on the birth date and center abbreviation (and not patient initials). The Sponsor will be the owner of the data. Data will be kept for 20 years.

The Participating Investigator and the Participating Site shall treat all information and data relating to the Study disclosed to Participating Site and/or Investigator in this study as confidential and shall not disclose such information to any third parties or use such information for any purpose other than the performance of the Study.

The collection, processing, and disclosure of personal data, such as patient health and medical information are subject to compliance with applicable personal data protection and the processing of personal data legislation (including but not limited to the European Union Directive 95/46/EC).

Champalimaud Foundation takes out the appropriate insurance.

Eligibility criteria: Inclusion Criteria:

* Histologically breast cancer (stage 0-III); scheduled for neoadjuvant treatment (cohort A - chemotherapy; cohort B - endocrine therapy)
* Women aged ≥ 18 years; nonpregnant
* Do not be involved in any structured exercise program in the past 6 months
* Medical approval to participate in the study
* Willingness to attend exercise sessions

Exclusion Criteria:

* Treated for any cancer in the past 5 years (except basal cancer)
* Uncontrolled heart disease (heart failure, uncontrolled coronary heart disease, and uncontrolled hypertension, cardiac disease)
* Diabetes mellitus
* Lung condition (chronic obstructive or restrictive pulmonary disease)
* Psychological disorders (dementia, Alzheimer, and Parkinson Disease)
* Severe disability, or other medical condition that prevents from exercise training
* Alcohol or drugs abuse

Primary outcomes:
measure: Changes from baseline Ki67% at the end of the intervention
timeFrame: 4-6 months
Secondary outcomes:
measure: Changes in body mass index (BMI) from baseline to T1 and T2
timeFrame: 4-6 months
measure: Changes in hip circumferences from baseline to T1 and T2
timeFrame: 4-6 months
measure: Changes in waist circumferences from baseline to T1 and T2
timeFrame: 4-6 months
measure: Changes in bone mineral density from baseline to T1 and T2
timeFrame: 4-6 months
measure: Changes in lean body mass from baseline to T1 and T2
timeFrame: 4-6 months
measure: Changes in phase angle from baseline to T1, T2, T3, T4, T5, T6
timeFrame: 4-6 months
measure: Changes in resting metabolic rate from baseline to the end of the intervention
timeFrame: 4-6 months
measure: Changes in peak oxygen content from baseline to the end of the intervention
timeFrame: 4-6 months
measure: Changes from baseline to T1 and T2 in upper limb strength
timeFrame: 4-6 months
measure: Changes from baseline to T1 and T2 in lower limb strength
timeFrame: 4-6 months
measure: Change from baseline to T1 and T2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Functional Scale Scores
timeFrame: 4-6 months
measure: Change from baseline to T1 and T2 in European Organization for Research and Treatment of Cancer Breast Cancer Module (EORTC QLQ BR23) Functional Scale Scores
timeFrame: 4-6 months
Other outcomes:
measure: Changes from baseline to T1 and T2 in Fatigue-FACIT scale
timeFrame: 4-6 months
measure: Changes in depression and anxiety from baseline to T1 and T2
timeFrame: 4-6 months
measure: Subjective Changes in sleep quality from baseline to T1 and T2
timeFrame: 4-6 months
measure: Objective Changes in sleep quality from baseline to T1 and T2
timeFrame: 4-6 months
measure: Changes from baseline physical activity and sedentary time at T1, T2, T3, T4, T5, T6
timeFrame: 4-6 months
measure: Changes in tumor size from baseline to the end of the intervention
timeFrame: 4-6 months
measure: Changes from baseline tumor hypoxia at the end of the intervention
timeFrame: 4-6 months
measure: Changes from baseline tumor infiltrating lymphocytes at the end of the intervention
timeFrame: 4-6 months
measure: Changes in fasting glucose from baseline to the end of the intervention
timeFrame: 4-6 months
measure: Changes in lipid profile from baseline to the end of the intervention
timeFrame: 4-6 months
measure: Changes in inflammatory profile from baseline to the end of the intervention
timeFrame: 4-6 months
measure: Changes in arterial health from baseline to the end of the intervention
timeFrame: 4-6 months
measure: Changes in cardiac health from baseline to the end of the intervention
timeFrame: 4-6 months
measure: Changes from baseline mitochondrial respiration at the end of the intervention
timeFrame: 4-6 months
Locations:
city: Lisbon
country: Portugal
facility: Faculdade de Motricidade Humana - Universidade de Lisboa
state: Cruz-Quebrada
city: Lisboa
country: Portugal
facility: Fundação Champalimaud
Study officials:
affiliation: Faculdade de Motricidade Humana - Universidade de Lisboa
name: Inês R. Correia, MSc
role: STUDY_CHAIR
References: