Clinical trial NCT04623554: Pre-operative Exercise During Neoadjuvant Chemotherapy in Patients With Breast Cancer
Official title: Neo-train: Pre-operative Exercise During Neoadjuvant Chemotherapy in Patients With Breast Cancer - a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: Prehabilitation
Pre-operative exercise
Breast cancer
Tumour regression
Neoadjuvant chemotherapy
Lead sponsor: Zealand University Hospital
Sponsor class: OTHER
Collaborators: name: Danish Cancer Society
name: University Hospital Southampton NHS Foundation Trust
name: Region Zealand
name: Naestved, Slagelse and Ringsted Hospitals
First posted: 2020-11-10
Enrollment: 102
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial with an intervention arm and a control arm
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: Inclusion Criteria:

* Patients newly diagnosed with histologically verified breast cancer and scheduled for neoadjuvant chemotherapy
* Female gender
* Aged ≥ 18 years old
* Signed informed consent

Exclusion Criteria:

* 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

Primary outcomes:
measure: Tumour size
timeFrame: 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.
Secondary outcomes:
measure: Relative dose intensity of neoadjuvant chemotherapy
timeFrame: Baseline to time of breast surgery estimated up to 30 weeks
measure: Number of participants with neoadjuvant chemotherapy dose reductions
timeFrame: Baseline to time of breast surgery estimated up to 30 weeks
measure: Number of participants with neoadjuvant chemotherapy dose delays
timeFrame: Baseline to time of breast surgery estimated up to 30 weeks
measure: Number of participants with early discontinuation of neoadjuvant chemotherapy
timeFrame: Baseline to time of breast surgery estimated up to 30 weeks
measure: Number of hospital admissions during neoadjuvant chemotherapy
timeFrame: Baseline to time of breast surgery estimated up to 30 weeks
measure: Total length of hospital admissions during neoadjuvant chemotherapy
timeFrame: Baseline to time of breast surgery estimated up to 30 weeks
measure: Changes in total body mass
timeFrame: Baseline, during the week before breast surgery, 3 months after breast surgery
measure: Changes in lean body mass
timeFrame: Baseline, during the week before breast surgery, 3 months after breast surgery
measure: Changes in fat mass
timeFrame: Baseline, during the week before breast surgery, 3 months after breast surgery
measure: Changes in physical fitness
timeFrame: Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
measure: Changes in muscle strength
timeFrame: Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
measure: Changes in physical function
timeFrame: Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
measure: Changes in level of physical activity
timeFrame: Baseline, during the week before breast surgery, 3 months after breast surgery
measure: Changes in health-related quality of life
timeFrame: Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
measure: Changes in general anxiety
timeFrame: Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
measure: Changes in depression
timeFrame: Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
measure: Changes in psychological distress
timeFrame: Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
measure: Post-operative referral to and participation in municipal rehabilitation programs
timeFrame: Breast surgery to 3 months after breast surgery
measure: Tumour size
timeFrame: 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
measure: Tumour size
timeFrame: At time of breast surgery estimated to take place within 30 weeks from baseline
measure: Pathological response grade
timeFrame: At time of breast surgery estimated to take place within 30 weeks from baseline
measure: Tumour infiltrating lymphocyte population
timeFrame: Baseline (pre-chemotherapy) to time of breast surgery estimated up to 30 weeks
measure: Tumour vascularity
timeFrame: Baseline (pre-chemotherapy) to time of breast surgery estimated up to 30 weeks
measure: Liquid biopsies
timeFrame: Baseline, approximately week 7, 13 and 19, 3 months after breast surgery
measure: Metabolic and inflammatory markers
timeFrame: Baseline, approximately week 13 and 19, 3 months after breast surgery
measure: Cytokines
timeFrame: Baseline, approximately week 13 and 19, 3 months after breast surgery
measure: Cell proliferation
timeFrame: Approximately between week 1-4 during neoadjuvant chemotherapy and within 6 weeks before breast surgery
measure: Recurrence
timeFrame: Breast surgery to up to 10 years follow-up after breast surgery
measure: Survival
timeFrame: Breast surgery to up to 10 years follow-up after breast surgery
Other outcomes:
Locations:
city: Naestved
country: Denmark
facility: Department of Clinical Oncology and Palliative Care, Zealand University Hospital
Study officials:
affiliation: Zealand University Hospital
name: Susanne Dalton, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kjeldsted E, Ammitzboll G, Jorgensen LB, Lodin A, Bojesen RD, Ceballos SG, Rosthoj S, Laenkholm AV, Skou ST, Jack S, Gehl J, Dalton SO. Neo-train: study protocol and feasibility results for a two-arm randomized controlled trial investigating the effect of supervised exercise during neoadjuvant chemotherapy on tumour response in patients with breast cancer. BMC Cancer. 2023 Aug 19;23(1):777. doi: 10.1186/s12885-023-11284-5.