Clinical trial NCT05184582: Physical Exercise During Preoperative Chemotherapy for Breast Cancer
Official title: Physical Exercise During Neoadjuvant Chemotherapy for Breast Cancer as a Means to Increase Pathological Complete Response Rates: the Randomized Neo-ACT Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
First posted: 2022-01-11
Enrollment: 712
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization to supervised high-intensity interval training during neoadjuvant chemotherapy or usual information about physical activity.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pathological complete response
timeFrame: 5-6 months
Secondary outcomes:
measure: Global health-related quality of life
timeFrame: baseline, after 1 and 2 years
measure: Breast cancer-related quality of life
timeFrame: baseline, after 1 and 2 years
measure: Self-reported physical activity
timeFrame: baseline, pre-surgery, 1- and 2-year follow-up
measure: Chemotherapy completion rate
timeFrame: 1 year
measure: Cumulative chemotherapy dosage
timeFrame: 1 year
measure: Objective cognitive dysfunction
timeFrame: baseline and 1 year
measure: Sick leave
timeFrame: pre-surgery and at 1- and 2-year follow-up
measure: Device-measured physical activity level
timeFrame: baseline and 5-6months (pre surgery)
measure: Muscle strength
timeFrame: baseline and 5-6 months
measure: Handgrip strength
timeFrame: baseline and 5-6 months
measure: Cardiorespiratory fitness
timeFrame: baseline and 5-6 months (pre-surgery)
measure: Radiological tumour response
timeFrame: 5-6 months
measure: Residual Cancer Burden (RCB)
timeFrame: 5-6 months
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Cabrini Health
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
city: Lidköping
country: Sweden
facility: Skaraborgs sjukhus
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Stockholm
country: Sweden
facility: Capio St Görans Hospital
city: Stockholm
country: Sweden
facility: Southern General Hospital
city: Sundsvall
country: Sweden
facility: Sundsvall Hospital
city: Umeå
country: Sweden
facility: Umeå University Hospital
city: Västerås
country: Sweden
facility: Västmanlands Hospital
city: Edinburgh
country: United Kingdom
facility: Edinburgh Napier University
state: Scotland
city: London
country: United Kingdom
facility: Royal Marsden
Study officials:
affiliation: Karolinska Institutet
name: Jana de Boniface
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Boniface J, Altena R, Haddad Ringborg C, Bolam KA, Wengstrom Y. Physical exercise during neoadjuvant chemotherapy for breast cancer as a mean to increase pathological complete response rates: Trial protocol of the randomized Neo-ACT trial. PLoS One. 2022 Oct 13;17(10):e0274804. doi: 10.1371/journal.pone.0274804. eCollection 2022.