Effects of Exercise in Patients With Metastatic Breast Cancer

Study Overview
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Brief Summary
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Currently, the effect of exercise on metastatic breast cancer has not been extensively studied, even though the benefits are evident in the curative setting. The investigators designed the EFFECT study to assess the effects of a 9-month structured and individualised exercise intervention in 350 patients with metastatic breast cancer (stage IV) on cancer-related physical fatigue, Health-Related Quality of Life (HRQoL), and other disease and treatment-related side effects at six months (primary endpoint).

Detailed Description
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The EFFECT study is a multicentre, randomised controlled trial. The intervention group will participate in a 9-month exercise intervention. The exercise program will start with a 6-month period, where patients participate in a supervised multimodal exercise program twice a week supplemented with unsupervised exercises. The multimodal exercise program comprises aerobic-, resistance- and balance components. After completing the initial six-month period, one supervised session will be replaced by one unsupervised session until month nine. Unsupervised exercises will be supported by an activity tracker (FitBit) and an exercise App specifically designed for the EFFECT trial. Patients randomized to the control group will also receive an activity tracker (like the intervention group). The investigators will advice control patients to avoid inactivity and be as physically active as current abilities and conditions allow, with the aim to progress towards being physically active for 150min/week in line with the current exercise guidelines.

Official Title
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Effects of Structured and Individualized Exercise in Patients With Metastatic Breast Cancer on Fatigue and Quality of Life

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Behavioral: Supervised exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of breast cancer stage IV ECOG (Eastern Cooperative Oncology Group scale) performance status ≤ 2 Able and willing to perform the exercise program and wear the activity tracker Exclusion Criteria: A potential subject who meets any of the following criteria is not eligible for enrolment into this study: Unstable bone metastases inducing skeletal fragility as determined by the treating clinician Untreated symptomatic known brain metastasis Estimated life expectancy < 6 months as determined by the treating clinician Serious active infection Too physically active (i.e. >210 minutes/week of moderate-to-vigorous intentional exercise Severe neurologic or cardiac impairment according ACSM criteria Uncontrolled severe respiratory insufficiency as determined by the treating clinician or if the patient is dependent on oxygen suppletion in rest or during exercise Uncontrolled severe pain Any other contraindications for exercise as determined by the treating physician Any circumstances that would impede adherence to study requirements or ability to give informed consent, as determined by the treating clinician Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Supervised exercise group<br>The intervention group will participate in a 9-month exercise intervention. The exercise program will start with a 6-month period, where patients participate in a supervised multimodal exercise program twice a week supplemented with unsupervised exercises. The multimodal exercise program comprises aerobic-, resistance- and balance components. After completing the initial six-month period, one supervised session will be replaced by one unsupervised session until month nine. Unsupervised exercises will be supported by an activity tracker (FitBit) and an exercise App specifically designed for the EFFECT trial | Behavioral: Supervised exercise<br>* An individualised exercise programme supervised by a trained instructor<br>|
| No Intervention: Control group<br>Patients randomized to the control group will also receive an activity tracker (like the intervention group). We will advice control patients to avoid inactivity and be as physically active as current abilities and conditions allow, with the aim to progress towards being physically active for 150min/week in line with the current exercise guidelines. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cancer-related physical fatigue | Physical fatigue measured with the EORTC QLQ-FA12 | 0- 6 months (measured at baseline, 3 and 6 months) | 
| Health-related Quality of Life | Disease specific HRQoL measured with the EORTC QLQ-C30 Summary Score | 0- 6 months (measured at baseline, 3 and 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Separate HRQoL domains and Summary Score | EORTC QLQ-C30 function and symptom scores scores | 0-9 months | 
| Cancer-related fatigue | EORTC QLQ-FA12 scores | 0-9 months | 
| Breast cancer specific symptoms | EORTC QLQ-BR45 | 0-9 months | 
| Anxiety, depression | PHQ-4 | 0-9 months | 
| Sleep | PSQI | 0-9 months | 
| Pain: severity and its impact on functioning. | BPI | 0-9 months | 
| Neuropathic pain | painDETECT | 0-9 months | 
| Pain Catastrophizing | PCS | 0-9 months | 
| Treatment-related toxicities grade≥3 | Common Toxicity Criteria for adverse events (CTCAE) | 0-9 months | 
| Weight | weight measured in KG | 0-6 months | 
| Height | Height measured in meters | 0-6 months | 
| Waist circumference | waist circumference measured in cm | 0-6 months | 
| Body composition (fat free mass and fat mass) | Bioelectrical impedance analysis (BIA), add-on in some centers (not obligatory): DEXA | 0-6 months | 
| Physical activity (subjective) | Questionnaire | 0-6-9 months | 
| Physical activity (objective) | activity tracker | 0-6-9 months | 
| Resting heart rate | Resting heart rate | 0-6 months | 
| Blood pressure | Blood pressure (diastolic and systolic) measured at rest | 0-6 months | 
| Physical performance | Short Physical Performance Battery, handgrip- and leg strength test | 0-6 months | 
| Physical fitness | Steep ramp test and endurance cycle test, add-on (not obligatory): CPET | 0-6 months | 
| Work status/ healthcare resources consumption | iPCQ/iMCQ | 0-9 months | 
| Intervention costs | Cost analyses | 0-9 months | 
| Health status | EQ-5D-5L | 0-9 months | 
| Satisfaction with exercise intervention | Self-developed questionnaire | 0-9 months | 
| Biomarkers (systemic inflammation, growth factors, blood/brain barrier modulators) | Blood samples (plasma, serum, buffy coat and peripheral blood mononuclear cells (PBMC) ) | 0-6 months | 
| Disease control | Progress or disease control of the breast cancer will be derived from medical records and/or the cancer registry | 0-9 months | 
| Cancer treatment | The type and duration of cancer treatment during the study will be derived from medical records and/or the cancer registry | 0-9 months | 
| Quality of working life | QWLQ-CS (add-on in several centers) | 0-9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exercise, cancer-related fatigue, quality of life