The Neo-Train study is a randomized controlled trial investigating the effects of supervised pre-operative aerobic and resistance exercise in patients with breast cancer during neoadjuvant chemotherapy.
The long neoadjuvant chemotherapy period in patients with breast cancer brings a time window of opportunity to investigate the potential of pre-operative exercise to increase treatment efficacy with improved tumour regression. A possible improvement in chemotherapy completion, lift in physical function, alleviated toxicities as well as changes in biological markers can also be investigated. 120 patients with newly diagnosed breast cancer who start neoadjuvant chemotherapy will be randomized to the intervention arm (n=60) and control arm (n=60). Participants in the intervention arm will be prescribed a prehabilitation program consisting of thrice weekly combined supervised aerobic and resistance exercise during the neoadjuvant chemotherapy period. Participants will be screened for psychological distress four times and in case of moderate-severe distress be advised to visit the local Cancer Society Support Center where participants will be assessed and offered free services based on their psychosocial needs and available offers. Participants in the control arm will receive usual care. Outcomes will be measured at baseline (diagnosis), during neoadjuvant chemotherapy, during the week before breast surgery, at breast surgery and at 3 months follow up. The participants will receive the recommended neoadjuvant chemotherapy regimens in Denmark - currently up to 24 weeks. With expected chemotherapy dose delays, the time of breast surgery is expected to be within 30 weeks from baseline. The treatment plans will be individually modified based on tumour response and expected side effects to treatment. A subgroup of participants may change neoadjuvant chemotherapy regimen and be referred to breast surgery early. In these participants, the last measurement during chemotherapy will be used, and the 3 months follow up measurement will still be scheduled at 3 months after breast surgery. The study procedures will be pre-tested in a pilot study with 6 patients who will all receive the prehabilitation program.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
SINGLE
Enrollment
102
The prehabilitation program includes combined high-intensity interval training on a cycle ergometer and machine-based resistance exercise of large muscle groups supervised by a physiotherapist. Exercise sessions will take place in physiotherapy departments at local hospitals or in municipality rehabilitation centres 3 times a week during the neoadjuvant chemotherapy period and ending in the week before breast surgery (maximum estimated 29 weeks depending on number of chemotherapy cycles, dose delays and time of breast surgery). Participants will be screened for psychological distress four times and in case of moderate-severe distress be advised to visit the local Cancer Society Support Center where participants will be assessed and offered free services based on their psychosocial needs and available offers. Participation will be monitored.
Department of Clinical Oncology and Palliative Care, Zealand University Hospital
Næstved, Denmark
Tumour size
Change in the maximum diameter of the tumour visualized by magnetic resonance imaging (MRI).
Time frame: Sequential MRI scans follow the individual treatment plan in a period of up to 30 weeks from baseline (diagnostic MRI before start of neoadjuvant chemotherapy) to MRI performed by the end of the course of neoadjuvant chemotherapy before breast surgery.
Relative dose intensity of neoadjuvant chemotherapy
Relative dose intensity in percentage defined as the ratio of received mg/m2 per week compared to planned mg/m2 per week according to standard guidelines.
Time frame: Baseline to time of breast surgery estimated up to 30 weeks
Number of participants with neoadjuvant chemotherapy dose reductions
Measured in percentage
Time frame: Baseline to time of breast surgery estimated up to 30 weeks
Number of participants with neoadjuvant chemotherapy dose delays
Measured in percentage
Time frame: Baseline to time of breast surgery estimated up to 30 weeks
Number of participants with early discontinuation of neoadjuvant chemotherapy
Measured in percentage
Time frame: Baseline to time of breast surgery estimated up to 30 weeks
Number of hospital admissions during neoadjuvant chemotherapy
Measured in percentage
Time frame: Baseline to time of breast surgery estimated up to 30 weeks
Total length of hospital admissions during neoadjuvant chemotherapy
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Measured in days
Time frame: Baseline to time of breast surgery estimated up to 30 weeks
Changes in total body mass
Changes from baseline measured by bioelectrical impedance analysis.
Time frame: Baseline, during the week before breast surgery, 3 months after breast surgery
Changes in lean body mass
Changes from baseline measured by bioelectrical impedance analysis.
Time frame: Baseline, during the week before breast surgery, 3 months after breast surgery
Changes in fat mass
Changes from baseline measured by bioelectrical impedance analysis.
Time frame: Baseline, during the week before breast surgery, 3 months after breast surgery
Changes in physical fitness
Changes in VO2 max estimated from maximum power output from baseline measured by a progressive cycle ergometer test (watt max test).
Time frame: Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
Changes in muscle strength
Changes in 1 repetition maximum strength from baseline measured on leg press and pull down.
Time frame: Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
Changes in physical function
Changes in hand grip strength from baseline measured by hand-held dynamometer in kilograms. Maximum kilograms obtained of 3 measurements on each hand.
Time frame: Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
Changes in level of physical activity
Changes in activity data measured by a wearable objective measurement device.
Time frame: Baseline, during the week before breast surgery, 3 months after breast surgery
Changes in health-related quality of life
Changes in self-reported health-related quality of life from baseline assessed on the Functional Assessment of Cancer Therapy - Breast Cancer (FACT-B).
Time frame: Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
Changes in general anxiety
Changes in self-reported general anxiety from baseline assessed on the Generalised Anxiety Disorder 7-item (GAD-7).
Time frame: Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
Changes in depression
Changes in self-reported depression from baseline assessed on the Patient Health Questionnaire-9 (PHQ-9).
Time frame: Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
Changes in psychological distress
Changes in self-reported psychological distress from baseline assessed on the Distress Thermometer (DT).
Time frame: Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
Post-operative referral to and participation in municipal rehabilitation programs
Frequency of participants referred to municipal rehabilitation, participation and types of activities attended identified from a self-reported questionnaire.
Time frame: Breast surgery to 3 months after breast surgery
Tumour size
Assessed by doctors' clinical examination of the breast.
Time frame: Sequential clinical examinations of the breast following the individual treatment plan in a period of up to 30 weeks from baseline to time of breast surgery
Tumour size
Measured by a pathologist from the tumour surgical specimen at breast surgery.
Time frame: At time of breast surgery estimated to take place within 30 weeks from baseline
Pathological response grade
Assessed by a pathologist from the tumour surgical specimen at breast surgery.
Time frame: At time of breast surgery estimated to take place within 30 weeks from baseline
Tumour infiltrating lymphocyte population
Description of tumour infiltrating lymphocyte population (percentage of cells) evaluated by a pathologist from the tumour biopsy specimen taken before chemotherapy and tumour surgical specimen at breast surgery.
Time frame: Baseline (pre-chemotherapy) to time of breast surgery estimated up to 30 weeks
Tumour vascularity
Description of tumour vascularity density and structure evaluated by a pathologist from the tumour biopsy specimen taken before chemotherapy and tumour surgical specimen at breast surgery.
Time frame: Baseline (pre-chemotherapy) to time of breast surgery estimated up to 30 weeks
Liquid biopsies
Changes in cell free DNA from blood samples. Furthermore, circulating tumour DNA will be investigated if possible.
Time frame: Baseline, approximately week 7, 13 and 19, 3 months after breast surgery
Metabolic and inflammatory markers
Changes in glucose, hba1c, zinc, magnesium, phosphate and C reactive protein (CRP) levels from blood samples.
Time frame: Baseline, approximately week 13 and 19, 3 months after breast surgery
Cytokines
Changes in cytokines from blood samples before, during and after neoadjuvant chemotherapy.
Time frame: Baseline, approximately week 13 and 19, 3 months after breast surgery
Cell proliferation
In vitro cell proliferation response with sera collected from blood samples before and after exercise.
Time frame: Approximately between week 1-4 during neoadjuvant chemotherapy and within 6 weeks before breast surgery
Recurrence
Incidence of breast cancer recurrence in percent
Time frame: Breast surgery to up to 10 years follow-up after breast surgery
Survival
Risk of mortality
Time frame: Breast surgery to up to 10 years follow-up after breast surgery