Breast Cancer
Conditions
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.
Interventions
BEHAVIORALPhysical training
Participants randomized to the exercise group will complete two structured 60-min exercise sessions per week from initiation of NACT to surgery (approx. five months).
Sponsors
Karolinska Institutet
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomization to supervised high-intensity interval training during neoadjuvant chemotherapy or usual information about physical activity.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response | 5-6 months | Absence of residual invasive tumor in breast and axilla at surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscle strength | baseline and 5-6 months | hypothetical 1-RM maximal leg muscle strength test |
| Handgrip strength | baseline and 5-6 months | handgrip strength test |
| Cardiorespiratory fitness | baseline and 5-6 months (pre-surgery) | Åstrand submaximal cycle test |
| Radiological tumour response | 5-6 months | RECIST |
| Residual Cancer Burden (RCB) | 5-6 months | Degree of tumor response to NACT |
| Self-reported physical activity | baseline, pre-surgery, 1- and 2-year follow-up | Modified Godin Leisure Time Physical activity questionnaire |
| Device-measured physical activity level | baseline and 5-6months (pre surgery) | Fit-bit tracker |
| Cumulative chemotherapy dosage | 1 year | total dose of NACT received to account for potential dose reduction |
| Objective cognitive dysfunction | baseline and 1 year | online neuropsychological test (Amsterdam Cognition Scan) |
| Sick leave | pre-surgery and at 1- and 2-year follow-up | Patient-reported absence from work |
| Global health-related quality of life | baseline, after 1 and 2 years | assessed by the EORTC QLQ-C30 questionnaire |
| Breast cancer-related quality of life | baseline, after 1 and 2 years | assessed by the EORTC QLQ-B23 questionnaire |
| Chemotherapy completion rate | 1 year | proportion of participants receiving the planned number of treatments |
Countries
Australia, Finland, Sweden, United Kingdom
Contacts
Primary ContactJana de Boniface
Backup ContactCecilia Haddad Ringborg
Outcome results
None listed