Attenuating Cancer Treatment-related Toxicity in Oncology Patients With a Tailored Physical Exercise Program

Study Overview
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Brief Summary
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The aim of this study is to determine if therapeutic exercise before anticancer treatment will mitigate the onset or extent of cardiotoxicity comparing to therapeutic exercise performed during anticancer treatment.

Detailed Description
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The positive relationship between physical exercise and cancer is widely justified in the literature, but an emerging research line warns of its capacity to improve the effectiveness and reduce the toxicity of cancer treatment (responsible for the appearance of side effects and comorbidities), that overload the health care system. To date, there is a lack of knowledge in different subjects: the possibility of implementing individualized exercise programs in clinical environment to mitigate the side effects of cancer treatment; the best moment in natural history of the disease to perform therapeutic exercise; and a tailored dose of exercise that maximizes its benefits. In this context, the present study will evaluate the effects of a therapeutic exercise program conducted previously at the beginning of the cancer treatment, in the treatments' toxicity against the same program conducted during cancer treatments in women with breast cancer, and its positive effects on both clinical and biological variables and their possible impact on disease-free survival. This study will be conducted in 3 phases with 110 participants in total: phase 1: a pilot study be carried out to check the feasibility of the proposed physical exercise program; phase 2: to test the effectiveness of the program ATOPE performed prior to surgical medical treatment against the same made during treatment, with a randomized controlled clinical trial; and phase 3: in which it will be integrated into the health service and a larger project will be requested at the international level.

Official Title
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Attenuating Cancer Treatment-related Toxicity in Oncology Patients With a Tailored Physical Exercise Program: Study Protocol of the ATOPE Trial in Women Recently Diagnosed With Breast Cancer

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Other: ATOPE-B
* Other: ATOPE-I


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older Breast cancer diagnosis I-III stage On the waiting list to anticancer medical treatment (at least surgery, chemotherapy and radiotherapy. If they meet other criteria which predisposes to higher toxicity. Have signed informed consent. Have medical clearance for participation. Exclusion Criteria: Patient underwent previous cancer treatments. Patients were previously diagnosed with cancer. Pregnant patients. Patients performing other type of therapeutic exercise at diagnosis time with an intake >or = to 150 moderate-intensity or 75 min of vigorous-intensity a day. Therapeutic exercise practice not recommended because psychiatric or cognitive disorders or cute or chronic condition that prevents exercise (advanced lung disease, oxygen requirement, stenosis >70%, metastasis etc.).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATOPE-B<br>An adapted therapeutic exercise program performed before medical treatment. 18 bouts of 1'5 hours multimodal components: aerobic, strength and fascial release exercises. Bout frequency will be adapted to the recovery status of each patient (heart rate variability training parameters and patient perception). | Other: ATOPE-B<br>* Patients will perform therapeutic exercise before medical treatment and will follow the usual care after medical treatment.<br>* Other names: Therapeutic exercise before medical treatment;|
| Active Comparator: ATOPE-I<br>An adapted therapeutic exercise program performed during medical treatment. 18 bouts of 1'5 hours multimodal components: aerobic, strength and fascial release exercises. Bout frequency will be adapted to the recovery status of each patient (heart rate variability training parameters and patient perception). | Other: ATOPE-I<br>* Patients will follow usual care before medical treatment and will perform therapeutic exercise after medical treatment.<br>* Other names: Therapeutic exercise during medical treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular ejection fraction | To assess cardiac toxicity by echocardiography | Participants will be followed over 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular events | Number of cardiovascular events registered in a diary | Participants will be followed over 12 months | 
| Resting heart rate | To assess cardiac function by a Holter | Participants will be followed over 12 months | 
| Heart Rate variability | To assess cardiac autonomic system balance by a Holter | Participants will be followed over 12 months | 
| Muscle loss | To assess muscle mass loss by Inbody | Participants will be followed over 12 months | 
| Quality of life with the Quality of Life Questionnaire (QLQ)-C30 | With the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) version 3.0. It is used to asses quality of life. It contains 30 items with both multi-item scales and single-item measures. Values are assigned between 1 and 4 (1: not at all, 2: a little, 3: enough, 4: a lot) according to the patient's responses to the item, only in items 29 and 30 evaluate with a score of 1 to 7 (1: lousy, 7: excellent). The scores obtained are standardized and a score between 0 and 100 is obtained, which determines the level of cancer impact on the patient of each of the scales. The high values in the scales of global health and function state indicate a better CV, while in the scale of symptoms it would indicate a decrease in CV since it indicates the presence of symptoms associated with cancer. | Participants will be followed over 12 months | 
| Quality of life with the Quality of life Questionnaire (QLQ- BR23) a specific module. | European Organization for Research and Treatment of Cancer Breast Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23). It is a breast cancer module of EORTC QLQ-C30. This module contains 23 items assessing symptoms and side effects related to different treatment modalities, body image, sexuality, and future perspective. After the scoring procedures for the QLQ-C30, all scale and single-item scores are linearly transformed to a 0 to 100 scale. For the functional scales and single items (ie, body image, sexuality, and future perspective), higher scores represent a better level of functioning. For the symptom scales and single item, a higher score represents a higher level of symptoms. | Participants will be followed over 12 months but will not be assessed in baseline | 
| Chemotherapy regimen | type of chemotherapy agent used and number of sessions. | Participants will be followed over 12 months | 
| Chemotherapy doses modifications | delay of doses or reduction, total doses received from the total expected. | Participants will be followed over 12 months | 
| Early session termination. | Patient stopped receiving chemotherapy before last >=1 sessions. | Participants will be followed over 12 months | 
| Missing bouts due to adverse effects of chemotherapy | Adverse effects of chemotherapy treatment and if it was interrupted (>=3 missing consecutive bouts of exercise) | Participants will be followed over 12 months | 
| Number of hospitalizations. |  | Participants will be followed over 12 months | 
| Therapeutic exercise bout modification | >=1 bout that required a dose modification during the program and number of bouts modified in total. | Participants will be followed over 12 months | 
| Time to treatment failure | days from the start to the end of chemotherapy, if it was terminated for toxicity and/or tumor progression. | Participants will be followed over 12 months | 
| Program adverse effects reported by the participants. | Frequency of serious and non-serious events occurring during program. | Participants will be followed over 12 months | 
| Functional capacity | assessed by the 6-Minute Walking Test | Participants will be followed over 12 months | 
| Handgrip strength | assessed by a digital dynamometer: TKK 5101 Grip-D; Takey, Tokyo, Japan | Participants will be followed over 12 months | 
| Shoulder strength | assessed by an isokinetic test with an isokinetic dynamometer (HUMAC NORM) | Participants will be followed over 12 months | 
| Lower limb strength | assessed by an isokinetic test with an isokinetic dynamometer (HUMAC NORM) | Participants will be followed over 12 months | 
| Abdominal strength | assessed by an isokinetic test with an isokinetic dynamometer (HUMAC NORM) | Participants will be followed over 12 months | 
| Flexibility | assessed by the Modified sit-and-reach test | Participants will be followed over 12 months | 
| Waist and hip circumferences | assessed by an inelastic tape | Participants will be followed over 12 months | 
| Body composition | assessed by the InBody | Participants will be followed over 12 months | 
| Oxidative stress | Thiobarbituric acid reactive substances (TBARS) | Participants will be followed over 12 months | 
| Oxidative stress | carbonyls and 8-hydroxy-2' -deoxyguanosine (8-OHdG) | Participants will be followed over 12 months | 
| Inmune function | Number of lymphocytes: (cluster of differentiation (CD) 8 and 4 and regulatory T lymphocytes) | Participants will be followed over 12 months | 
| inflammation | C-reactive protein (CRP) | Participants will be followed over 12 months | 
| inflammation | interleukin (IL) 6 and 10 | Participants will be followed over 12 months | 
| inflammation | tumor necrosis factor (TNF) alpha | Participants will be followed over 12 months | 
| inflammation | insulin-like growth factor 1 (IGF-1) | Participants will be followed over 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast neoplasm, Breast cancer, therapeutic exercise, cardiotoxicity, muscle toxicity