Physical Exercise During Preoperative Chemotherapy for Breast Cancer

Breast Cancer Clinical Trial

— Neo-ACT  

Official title:

Physical Exercise During Neoadjuvant Chemotherapy for Breast Cancer as a Means to Increase Pathological Complete Response Rates: the Randomized Neo-ACT Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05184582
• Other study ID #: Neo-ACT
• Status: Recruiting
• Phase: N/A
• Start date: November 9, 2022
• Est. completion date: December 2027

Study information

• Verified date: March 2024
• Source: Karolinska Institutet
• Contact: Jana de Boniface
• Phone: +46702472305
• Email: jana.de-boniface[@]ki.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 712
• Est. completion date: December 2027
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Behavioral:
• Physical 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).

Locations

Country	Name	City	State
Australia	Cabrini Health	Melbourne
Finland	Helsinki University Hospital	Helsinki
Finland	Turku University Hospital	Turku
Sweden	Sahlgrenska University Hospital	Gothenburg
Sweden	Skaraborgs sjukhus	Lidköping
Sweden	Capio St Görans Hospital	Stockholm
Sweden	Karolinska University Hospital	Stockholm
Sweden	Southern General Hospital	Stockholm
Sweden	Sundsvall Hospital	Sundsvall
Sweden	Umeå University Hospital	Umeå
Sweden	Västmanlands Hospital	Västerås
United Kingdom	Edinburgh Napier University	Edinburgh	Scotland
United Kingdom	Royal Marsden	London

Sponsors (1)

Lead Sponsor	Collaborator
Karolinska Institutet

Countries where clinical trial is conducted

Australia,  Finland,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological complete response	Absence of residual invasive tumor in breast and axilla at surgery	5-6 months
Secondary	Global health-related quality of life	assessed by the EORTC QLQ-C30 questionnaire	baseline, after 1 and 2 years
Secondary	Breast cancer-related quality of life	assessed by the EORTC QLQ-B23 questionnaire	baseline, after 1 and 2 years
Secondary	Self-reported physical activity	Modified Godin Leisure Time Physical activity questionnaire	baseline, pre-surgery, 1- and 2-year follow-up
Secondary	Chemotherapy completion rate	proportion of participants receiving the planned number of treatments	1 year
Secondary	Cumulative chemotherapy dosage	total dose of NACT received to account for potential dose reduction	1 year
Secondary	Objective cognitive dysfunction	online neuropsychological test (Amsterdam Cognition Scan)	baseline and 1 year
Secondary	Sick leave	Patient-reported absence from work	pre-surgery and at 1- and 2-year follow-up
Secondary	Device-measured physical activity level	Fit-bit tracker	baseline and 5-6months (pre surgery)
Secondary	Muscle strength	hypothetical 1-RM maximal leg muscle strength test	baseline and 5-6 months
Secondary	Handgrip strength	handgrip strength test	baseline and 5-6 months
Secondary	Cardiorespiratory fitness	Åstrand submaximal cycle test	baseline and 5-6 months (pre-surgery)
Secondary	Radiological tumour response	RECIST	5-6 months
Secondary	Residual Cancer Burden (RCB)	Degree of tumor response to NACT	5-6 months