Effects of Exercise in Patients With Metastatic Breast Cancer (EFFECT)

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Behavioral: Supervised exercise

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 357
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anne May, PhD; Phone Number: 0031-88-7551132; Email: a.m.may@umcutrecht.nl
• Study Contact Backup: Name: Evelyn Monninkhof, PhD; Phone Number: 0031-88-7559379; Email: e.monninkhof@umcutrecht.nl

Study Locations

• Netherlands
  • Utrecht, Netherlands
    • University Medical Center Utrecht

Participation Criteria

Eligibility Criteria

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

Description

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

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: Supervised exercise group; 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; An individualised exercise programme supervised by a trained instructor
No Intervention: Control group; 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?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Exploratory outcome	0-60 months
Overall and breast-cancer specific survival	Exploratory outcome	0-60 months
Safety of exercise intervention	(Serious) Adverse events potentially related to the exercise intervention	0-9 months
Urinary incontinence	Exploratory outcome (add on in some centers) - measured with ICIQ-UI	0-9 months
Maximal isokinetic and isometric leg strength, muscle thickness of m. rectus femoris (RF) and m. vastus lateralis (VL)	Exploratory outcome (add on in one center) - Isokinetic and isometric legstrength measured with peak torque / Muscle thickness with ultrasound protocol	0-9 months

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: Karolinska Institutet; German Cancer Research Center; University Hospital Heidelberg; The Netherlands Cancer Institute; Australian Catholic University; German Sport University, Cologne; Medical University of Gdansk; Fundación Onkologikoa Fundazioa; Europa Donna; Nurogames GmbH, Cologne
• Investigators: Principal Investigator: Anne May, PhD, UMC Utrecht Julius Center

Publications and helpful links

General Publications

• Hiensch AE, Monninkhof EM, Schmidt ME, Zopf EM, Bolam KA, Aaronson NK, Belloso J, Bloch W, Clauss D, Depenbusch J, Lachowicz M, Pelaez M, Rundqvist H, Senkus E, Stuiver MM, Trevaskis M, Urruticoechea A, Rosenberger F, van der Wall E, de Wit GA, Zimmer P, Wengstrom Y, Steindorf K, May AM. Design of a multinational randomized controlled trial to assess the effects of structured and individualized exercise in patients with metastatic breast cancer on fatigue and quality of life: the EFFECT study. Trials. 2022 Jul 29;23(1):610. doi: 10.1186/s13063-022-06556-7.

Helpful Links

• Website of the EFFECT study within the PREFERABLE project
• Twitter account PREFERABLE project

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2020
• Primary Completion (Actual): February 28, 2023
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: September 12, 2019
• First Submitted That Met QC Criteria: October 7, 2019
• First Posted (Actual): October 9, 2019

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: exercise; quality of life; cancer-related fatigue
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 19-524; NL69600.041.19 (Other Identifier: CCMO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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