Activity Program During Aromatase Inhibitor Therapy

Study Overview
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Brief Summary
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The primary aim of the trial is to investigate if a simple outdoor walking intervention, which is practicable under real-life conditions, beginning at the start of adjuvant aromatase inhibitor (AI) therapy, can prevent the occurrence of muscle or joint pain/stiffness in breast cancer patients.

Detailed Description
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After tumor removal, patients with hormone receptor positive breast cancer tumors often receive adjuvant endocrine treatment, with the use of an aromatase inhibitor (AI) being standard of care in the population of postmenopausal women. Common side effects of AI therapy are joint pain, muscle pain, stiffness, fatigue, hot flashes, and weight gain. Arthralgia and/or myalgia can result in lower physical activity and can negatively influence quality of life (QoL). In addition, muscle or joint pain/stiffness are among the main reasons for non-compliance and discontinuation of AI therapy. Because AI therapy is usually administered for 5 and sometimes even 10 years, this is a major clinical challenge. For breast cancer patients undergoing AI therapy, physical activity can provide potential benefit by reducing muscle/joint pain and fatigue and can thus improve QoL. The preventive effect of physical activity on AI side effects, however, remains elusive. In addition, activity programs to reduce AI side effects have so far mostly been rather complex. The primary aim of the trial is to investigate if a simple outdoor walking intervention, which is practicable under real-life conditions, beginning at the start of adjuvant AI therapy, can prevent the occurrence of muscle or joint pain/stiffness in breast cancer patients. Furthermore, this trial will assess the effect of physical activity on symptom burden in general and quality of life in patients receiving adjuvant AI therapy. During the follow-up phase, the trial will assess whether this intervention leads to a sustained change in lifestyle regarding activity, less pain, and better treatment adherence in the intervention group.

Official Title
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A 24 Weeks Activity Program in Patients With Early Breast Cancer Receiving Aromatase Inhibitor Therapy. A Multicenter Randomized Phase III Trial

Conditions
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Early Breast Cancer

Intervention / Treatment
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* Behavioral: Activity program
* Behavioral: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent according to Swiss law and ICH/GCP regulations before registration and prior to any trial specific procedures. Histologically confirmed hormone-receptor-positive newly diagnosed breast cancer, AJCC (American Joint Committee on Cancer) stage I-III Patient had tumor removal by breast conserving surgery or mastectomy, followed by chemotherapy (if indicated) and/or radiotherapy (if indicated) Patient is starting adjuvant first-line endocrine treatment with an AI alone (in postmenopausal women) or combined endocrine treatment with an AI and ovarian suppression with an LHRH-agonist (in premenopausal women) Patient completed the PRO Form Eligibility before registration Patient is fluent in German, Italian, or French Patient is willing to wear a wrist worn activity tracker for 24 weeks Female patient, age ≥ 18 years WHO performance status 0-2 Exclusion Criteria: Pre-existing severe medical conditions such as heart or lung problems or musculoskeletal conditions precluding participation in the physical activity program of moderate walking a total of 150 minutes per week as determined by the local investigator Mild, moderate, or severe pain (other than post-operative pain) in the last 24 hours due to muscle/joint pain on the BPI-SF single item worst pain (worst pain ≥3) within 7 days prior to registration Inoperable, locally advanced and/or metastatic breast cancer Active rheumatoid arthritis Neoadjuvant endocrine treatment with an AI NSAIDs, acetaminophen or opioids on a regular basis (> 1 time per week) Concurrent participation in other clinical trials or observational studies Any other serious psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the intervention and follow-up or affect patient compliance with trial procedures.

Ages Eligible for Study
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Minimum Age: 18 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Home-based walking intervention for 24 weeks + standard adjuvant AI therapy Physical activity according to standard recommendations for 24 weeks + standard adjuvant AI therapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: a) Home-based walking intervention<br>Home-based walking intervention, wearing a wrist worn activity tracker, for 24 weeks + standard adjuvant AI therapy | Behavioral: Activity program<br>* Home-based walking intervention, wearing a wrist worn activity tracker, for 24 weeks<br>|
| Active Comparator: b) Physical activity according to standard recommendations<br>Physical activity according to standard recommendations, wearing a wrist worn activity tracker (with no feedback about performed activity), for 24 weeks + standard adjuvant AI therapy | Behavioral: Control<br>* Physical activity according to standard recommendations, wearing a wrist worn activity tracker (with no feedback about performed activity), for 24 weeks + standard adjuvant AI therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of muscle or joint pain/stiffness as measured by BPI-SF single-item worst pain score | Muscle or joint pain/stiffness will be assessed at baseline, 3, 9, 12, 15, 18, 21, 24 weeks after randomization by the BPI-SF questionnaire. The BPI-SF is a 14-item self-administered questionnaire which is routinely used in clinical trials to assess pain severity and pain interference with daily activities in patients with cancer. Pain severity is assessed by four items including pain at its worst, least, average in the last 24 hours and now (current pain), each item being rated on a 0-10 scale. | Up to 24 weeks after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue | Fatigue will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0. | Baseline, 12 and 24 weeks and 1 and 2 years after randomization | 
| QoL: Physical scale (EORTC QLQ-C30) | Physical scale will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0. | Baseline, 12 and 24 weeks and 1 and 2 years after randomization | 
| QoL: Rose scale (EORTC QLQ-C30) | Role scale will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0. | Baseline, 12 and 24 weeks and 1 and 2 years after randomization | 
| QoL: Emotional scale (EORTC QLQ-C30) | Emotional scale will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0. | Baseline, 12 and 24 weeks and 1 and 2 years after randomization | 
| QoL: Cognitive scale (EORTC QLQ-C30) | Cognitive scale will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0. | Baseline, 12 and 24 weeks and 1 and 2 years after randomization | 
| QoL: Social functioning scale (EORTC QLQ-C30) | Cognitive scale will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0. | Baseline, 12 and 24 weeks and 1 and 2 years after randomization | 
| Nausea/Vomiting | Nausea/vomiting will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0. | Baseline, 12 and 24 weeks and 1 and 2 years after randomization | 
| Pain (EORTC QLQ-C30) | Pain will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0. | Baseline, 12 and 24 weeks and 1 and 2 years after randomization | 
| Global health status | Global health status will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0. | Baseline, 12 and 24 weeks and 1 and 2 years after randomization | 
| Dyspnoea | Dyspnoea will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0. | Baseline, 12 and 24 weeks and 1 and 2 years after randomization | 
| Insomnia | Insomnia will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0. | Baseline, 12 and 24 weeks and 1 and 2 years after randomization | 
| Appetite loss | Appetite loss will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0. | Baseline, 12 and 24 weeks and 1 and 2 years after randomization | 
| Constipation | Constipation will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0. | Baseline, 12 and 24 weeks and 1 and 2 years after randomization | 
| Diarrhoea | Diarrhoea will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0. | Baseline, 12 and 24 weeks and 1 and 2 years after randomization | 
| Financial difficulties | Financial difficulties will be assessed at baseline, during intervention phase and during follow-up phase using the corresponding symptom scale of the EORTC QLQ-C30 version 3.0. | Baseline, 12 and 24 weeks and 1 and 2 years after randomization | 
| Hot flashes | Hot flashes will be assessed at baseline, during intervention phase and during follow-up phase via the item 37 of the EORTC QLQ BR-23. | Baseline, 12 and 24 weeks and 1 and 2 years after randomization | 
| Intensity of muscle or joint pain/stiffness and its impact on everyday functioning | Severity of muscle or joint pain/stiffness will be measured by the four BPI pain severity items. Pain interference will be calculated as the mean of the seven interference items. | Baseline, 3, 9, 12, 15, 18, 21, 24 weeks and 1, 2 years after randomization | 
| Walking activity | During trial intervention phase, daily steps will be measured by a wrist worn activity tracker. | Baseline, 3, 9, 12, 15, 18, 21, 24 weeks after randomization | 
| AI treatment adherence (diary) | Adherence will be assessed by patient self-report (diary). | Baseline, 3, 9, 12, 15, 18, 21, 24 weeks. | 
| AI treatment adherence (questionnaire) | Adherence will be assessed by patient self-report (questionnaire completed at visits). | Baseline, 12, 24 weeks and 1, 2 years after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pedometer, early breast cancer, aromatase inhibitor therapy, activity program, physical activity, activity tracker, stepcounter