Pre-operative Exercise During Neoadjuvant Chemotherapy in Patients With Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Behavioral: Prehabilitation program
- Registration Number
- NCT04623554
- Lead Sponsor
- Zealand University Hospital
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 102
- Patients newly diagnosed with histologically verified breast cancer and scheduled for neoadjuvant chemotherapy
- Female gender
- Aged ≥ 18 years old
- Signed informed consent
- Patients ineligible for or who have declined to receive neoadjuvant chemotherapy
- Contraindications to magnetic resonance imaging (MRI)
- Physical or cognitive disabilities preventing exercise or physical testing
- Inability to read and understand Danish
- Based on clinical judgement, the physician assesses that the patient is not suitable for inclusion
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intervention arm Prehabilitation program Prehabilitation program
- Primary Outcome Measures
Name Time Method Tumour size 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. Change in the maximum diameter of the tumour visualized by magnetic resonance imaging (MRI).
- Secondary Outcome Measures
Name Time Method Changes in muscle strength Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery Changes in 1 repetition maximum strength from baseline measured on leg press and pull down.
Changes in total body mass Baseline, during the week before breast surgery, 3 months after breast surgery Changes from baseline measured by bioelectrical impedance analysis.
Changes in fat mass Baseline, during the week before breast surgery, 3 months after breast surgery Changes from baseline measured by bioelectrical impedance analysis.
Pathological response grade At time of breast surgery estimated to take place within 30 weeks from baseline Assessed by a pathologist from the tumour surgical specimen at breast surgery.
Number of participants with early discontinuation of neoadjuvant chemotherapy Baseline to time of breast surgery estimated up to 30 weeks Measured in percentage
Relative dose intensity of neoadjuvant chemotherapy Baseline to time of breast surgery estimated up to 30 weeks 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.
Number of participants with neoadjuvant chemotherapy dose reductions Baseline to time of breast surgery estimated up to 30 weeks Measured in percentage
Number of participants with neoadjuvant chemotherapy dose delays Baseline to time of breast surgery estimated up to 30 weeks Measured in percentage
Total length of hospital admissions during neoadjuvant chemotherapy Baseline to time of breast surgery estimated up to 30 weeks Measured in days
Changes in physical fitness Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery Changes in VO2 max estimated from maximum power output from baseline measured by a progressive cycle ergometer test (watt max test).
Tumour size At time of breast surgery estimated to take place within 30 weeks from baseline Measured by a pathologist from the tumour surgical specimen at breast surgery.
Number of hospital admissions during neoadjuvant chemotherapy Baseline to time of breast surgery estimated up to 30 weeks Measured in percentage
Tumour infiltrating lymphocyte population Baseline (pre-chemotherapy) to time of breast surgery estimated up to 30 weeks 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.
Liquid biopsies Baseline, approximately week 7, 13 and 19, 3 months after breast surgery Changes in cell free DNA from blood samples. Furthermore, circulating tumour DNA will be investigated if possible.
Cytokines Baseline, approximately week 13 and 19, 3 months after breast surgery Changes in cytokines from blood samples before, during and after neoadjuvant chemotherapy.
Changes in lean body mass Baseline, during the week before breast surgery, 3 months after breast surgery Changes from baseline measured by bioelectrical impedance analysis.
Changes in physical function Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery Changes in hand grip strength from baseline measured by hand-held dynamometer in kilograms. Maximum kilograms obtained of 3 measurements on each hand.
Post-operative referral to and participation in municipal rehabilitation programs Breast surgery to 3 months after breast surgery Frequency of participants referred to municipal rehabilitation, participation and types of activities attended identified from a self-reported questionnaire.
Metabolic and inflammatory markers Baseline, approximately week 13 and 19, 3 months after breast surgery Changes in glucose, hba1c, zinc, magnesium, phosphate and C reactive protein (CRP) levels from blood samples.
Cell proliferation Approximately between week 1-4 during neoadjuvant chemotherapy and within 6 weeks before breast surgery In vitro cell proliferation response with sera collected from blood samples before and after exercise.
Changes in level of physical activity Baseline, during the week before breast surgery, 3 months after breast surgery Changes in activity data measured by a wearable objective measurement device.
Changes in health-related quality of life Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery Changes in self-reported health-related quality of life from baseline assessed on the Functional Assessment of Cancer Therapy - Breast Cancer (FACT-B).
Changes in general anxiety Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery Changes in self-reported general anxiety from baseline assessed on the Generalised Anxiety Disorder 7-item (GAD-7).
Changes in depression Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery Changes in self-reported depression from baseline assessed on the Patient Health Questionnaire-9 (PHQ-9).
Tumour vascularity Baseline (pre-chemotherapy) to time of breast surgery estimated up to 30 weeks 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.
Survival Breast surgery to up to 10 years follow-up after breast surgery Risk of mortality
Changes in psychological distress Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery Changes in self-reported psychological distress from baseline assessed on the Distress Thermometer (DT).
Recurrence Breast surgery to up to 10 years follow-up after breast surgery Incidence of breast cancer recurrence in percent
Trial Locations
- Locations (1)
Department of Clinical Oncology and Palliative Care, Zealand University Hospital
🇩🇰Naestved, Denmark