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Physical Exercise During Preoperative Chemotherapy for Breast Cancer

Not Applicable
Recruiting
Conditions
Breast Cancer
Interventions
Behavioral: Physical training
Registration Number
NCT05184582
Lead Sponsor
Karolinska Institutet
Brief Summary

Neoadjuvant chemotherapy (NACT) is increasingly used in breast cancer. The best proof of NACT efficacy is pathological complete response (pCR), i.e. the absence of invasive tumour on post-NACT surgical histopathology. While it is known that physical exercise can help patients to better tolerate and complete often harsh cancer treatments, it is an emerging area of research to understand if and how exercise exerts anti-tumour effects and improves oncological outcomes.

The main aim of the Neo-ACT trial is to examine if a physical exercise intervention during NACT can increase pCR rates in breast cancer. Secondary aims are residual cancer burden, radiological tumour response, patient-related outcomes (health-related quality of life, physical activity), physiological outcomes (muscle strength, cardiorespiratory fitness), cancer treatment-related toxicities (cognitive dysfunction, chemotherapy completion rates) and long-term sick leave. Furthermore, the trial will explore how physical exercise affects anti-tumoral mechanisms inherent to therapy or host by hypothesis-generating translational analyses.

712 patients with primary invasive breast cancer will be randomized to either a supervised intervention of high-intensity interval and resistance training during NACT, supported by an exercise app, or to usual care, and followed for two years. Physical activity is meticulously tracked. By offering patients active involvement, the trial contributes strongly to the concept of personalized medicine.

Detailed Description

The Neo-ACT assesses the primary endpoint pathological complete response (pCR) and the secondary endpoints Residual Cancer Burden (RCB), objective tumour response (RECIST), all-cause, breast cancer-specific, and recurrence-free survival at 2, 5 and 10 years, health-related quality of life assessed by the EORTC QLQ-C30 and BR23 questionnaires, self-reported physical activity (Modified Godin Leisure Time Physical activity questionnaire), toxicity-related outcomes (chemotherapy completion rates, number of unplanned hospital admissions during NACT, objective cognitive dysfunction (Amsterdam Cognition Scan), cardiac toxicity and sick leave), device-measured physical activity level (Fitbit activity tracker), muscle strength (handgrip strength test and hypothetical 1-RM maximal leg muscle strength tests), and cardiorespiratory fitness (Ekblom-Bak submaximal cycle test).

Participants randomized to the exercise group will complete 120 min exercise sessions per week from initiation of NACT to surgery (approx. five months):

* Progressive home exercise program by an individualised mobile phone application, supported by local physiotherapists

* Initial exercise intensity individually tailored to each patient's fitness at baseline and rate of perceived exertion during the program and adapted if required

* Sessions will begin with a 3-minute moderate intensity (12-13 on Borg's Rate of Perceived Exertion (RPE) scale) warm-up.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
712
Inclusion Criteria
  • Patients with primary invasive breast cancer cT1-T3 cN0-2
  • Full tumour biology available before initiation of NACT
  • Oral and written consent
  • Age ≥ 18 years
Exclusion Criteria
  • Pregnancy or breast-feeding
  • Bilateral invasive breast cancer
  • The presence of musculoskeletal, neurological, respiratory, metabolic or cardiovascular conditions that may prevent safe completion of the exercise demands of the study
  • Currently performing equal to or more than 150 mins of moderate to high intensity aerobic exercise and 2 sessions per week of moderate intensity resistance exercise

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
InterventionPhysical trainingHigh-intensity interval and strength training during neoadjuvant chemotherapy
Primary Outcome Measures
NameTimeMethod
Pathological complete response5-6 months

Absence of residual invasive tumor in breast and axilla at surgery

Secondary Outcome Measures
NameTimeMethod
Global health-related quality of lifebaseline, after 1 and 2 years

assessed by the EORTC QLQ-C30 questionnaire

Sick leavepre-surgery and at 1- and 2-year follow-up

Patient-reported absence from work

Chemotherapy completion rate1 year

proportion of participants receiving the planned number of treatments

Cumulative chemotherapy dosage1 year

total dose of NACT received to account for potential dose reduction

Device-measured physical activity levelbaseline and 5-6months (pre surgery)

Fit-bit tracker

Handgrip strengthbaseline and 5-6 months

handgrip strength test

Breast cancer-related quality of lifebaseline, after 1 and 2 years

assessed by the EORTC QLQ-B23 questionnaire

Self-reported physical activitybaseline, pre-surgery, 1- and 2-year follow-up

Modified Godin Leisure Time Physical activity questionnaire

Muscle strengthbaseline and 5-6 months

hypothetical 1-RM maximal leg muscle strength test

Radiological tumour response5-6 months

RECIST

Objective cognitive dysfunctionbaseline and 1 year

online neuropsychological test (Amsterdam Cognition Scan)

Cardiorespiratory fitnessbaseline and 5-6 months (pre-surgery)

Åstrand submaximal cycle test

Residual Cancer Burden (RCB)5-6 months

Degree of tumor response to NACT

Trial Locations

Locations (13)

Cabrini Health

🇦🇺

Melbourne, Australia

Turku University Hospital

🇫🇮

Turku, Finland

Helsinki University Hospital

🇫🇮

Helsinki, Finland

Sahlgrenska University Hospital

🇸🇪

Gothenburg, Sweden

Skaraborgs sjukhus

🇸🇪

Lidköping, Sweden

Karolinska University Hospital

🇸🇪

Stockholm, Sweden

Southern General Hospital

🇸🇪

Stockholm, Sweden

Capio St Görans Hospital

🇸🇪

Stockholm, Sweden

Sundsvall Hospital

🇸🇪

Sundsvall, Sweden

Umeå University Hospital

🇸🇪

Umeå, Sweden

Edinburgh Napier University

🇬🇧

Edinburgh, Scotland, United Kingdom

Västmanlands Hospital

🇸🇪

Västerås, Sweden

Royal Marsden

🇬🇧

London, United Kingdom

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