Activity Program During Aromatase Inhibitor Therapy

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

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.

Study Overview

• Status: Completed
• Conditions: Early Breast Cancer
• Intervention / Treatment: Behavioral: Activity program; Behavioral: Control

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 375
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Aarau, Switzerland, 5001
    • Kantonsspital Aarau
  • Baden, Switzerland, 5404
    • Kantonsspital Baden
  • Basel, Switzerland, CH-4031
    • Universitätsspital Basel
  • Basel, Switzerland, 4052
    • Brustzentrum Basel - Praxis für ambulante Tumortherapie
  • Basel, Switzerland, 4051
    • CABA - Zentrum für Onkologie, Psychologie und Bewegung
  • Bern, Switzerland, 3010
    • Inselspital Bern
  • Bern, Switzerland, 3013
    • Hirslanden Brustzentrum Bern Biel
  • Chur, Switzerland, 7000
    • Kantonsspital Graubünden
  • Chur, Switzerland, 7000
    • Tumorzentrum ZeTuP Chur
  • Chêne-Bougeries, Switzerland, 1224
    • Clinique des Grangettes, Centre du sein
  • Frauenfeld, Switzerland, 8501
    • Brustzentrum Thurgau
  • Fribourg, Switzerland, 1700
    • Centre du sein Fribourg / Brustzentrum Freiburg
  • Genolier, Switzerland, 1272
    • Clinique De Genolier
  • Locarno, Switzerland, 6600
    • FOLM - Fondazione Oncologia Lago Maggiore
  • Lugano, Switzerland, 6900
    • Oncologia Varini&Calderoni&Christinat
  • Luzern, Switzerland, 6006
    • Hirslanden Klinik St. Anna
  • Luzerne, Switzerland, CH-6000
    • Kantonsspital Luzern
  • Manno, Switzerland, 8708
    • Onkologie Zentrum Spital Männedorf
  • Mendrisio, Switzerland, 6850
    • Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
  • Neuenhof, Switzerland, 2000
    • Hôpital neuchâtelois
  • Olten, Switzerland, 4600
    • Kantonsspital Olten
  • Rapperswil-Jona, Switzerland, 8640
    • Tumorzentrum ZeTuP Rapperswil-Jona
  • Saint Gallen, Switzerland, 9016
    • Brustzentrum Ostschweiz
  • Sargans, Switzerland, 7320
    • Rundum Onkologie am Bahnhofpark
  • Sion, Switzerland
    • Hopital de Sion
  • St. Gallen, Switzerland, 9006
    • Tumorzentrum ZeTUP
  • St. Gallen, Switzerland, CH-9007
    • Kantonsspital St. Gallen
  • Thun, Switzerland, 3600
    • Regionalspital Thun
  • Winterthur, Switzerland, 8401
    • Kantonsspital Winterthur, Brustzentrum
  • Zurich, Switzerland, 8001
    • Onkologie Bellevue
  • Zürich, Switzerland, 8091
    • Universitäts Spital Zürich
  • Zürich, Switzerland, 8008
    • Brustzentrum Zürich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: a) Home-based walking intervention; Home-based walking intervention, wearing a wrist worn activity tracker, for 24 weeks + standard adjuvant AI therapy	Behavioral: Activity program; Home-based walking intervention, wearing a wrist worn activity tracker, for 24 weeks
Active Comparator: b) Physical activity according to standard recommendations; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Swiss Group for Clinical Cancer Research
• Investigators: Study Chair: Friedemann Honecker, MD, Tumor- und Brustzentrum ZeTuP St.Gallen; Study Chair: Nicolette Hoefnagels, MSc, Tumor- und Brustzentrum ZeTuP St.Gallen

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2019
• Primary Completion (Actual): September 27, 2021
• Study Completion (Actual): June 8, 2023

Study Registration Dates

• First Submitted: December 14, 2018
• First Submitted That Met QC Criteria: December 20, 2018
• First Posted (Actual): December 24, 2018

Study Record Updates

• Last Update Posted (Actual): June 27, 2023
• Last Update Submitted That Met QC Criteria: June 26, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: physical activity; pedometer; activity tracker; early breast cancer; aromatase inhibitor therapy; activity program; stepcounter
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: SAKK 95/17

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No