Pre-operative Exercise During Neoadjuvant Chemotherapy in Patients With Breast Cancer

Breast Cancer Clinical Trial

— Neo-train  

Official title:

Neo-train: Pre-operative Exercise During Neoadjuvant Chemotherapy in Patients With Breast Cancer - a Randomized Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04623554
• Other study ID #: REG-074-2020
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 23, 2021
• Est. completion date: February 15, 2034

Study information

• Verified date: March 2024
• Source: Zealand University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 102
• Est. completion date: February 15, 2034
• Est. primary completion date: February 15, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Behavioral:
• Prehabilitation program
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.

Locations

Country	Name	City	State
Denmark	Department of Clinical Oncology and Palliative Care, Zealand University Hospital	Naestved

Sponsors (5)

Lead Sponsor	Collaborator
Zealand University Hospital	Danish Cancer Society, Naestved, Slagelse and Ringsted Hospitals, Region Zealand, University Hospital Southampton NHS Foundation Trust

Country where clinical trial is conducted

Denmark, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumour size	Change in the maximum diameter of the tumour visualized by magnetic resonance imaging (MRI).	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	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.	Baseline to time of breast surgery estimated up to 30 weeks
Secondary	Number of participants with neoadjuvant chemotherapy dose reductions	Measured in percentage	Baseline to time of breast surgery estimated up to 30 weeks
Secondary	Number of participants with neoadjuvant chemotherapy dose delays	Measured in percentage	Baseline to time of breast surgery estimated up to 30 weeks
Secondary	Number of participants with early discontinuation of neoadjuvant chemotherapy	Measured in percentage	Baseline to time of breast surgery estimated up to 30 weeks
Secondary	Number of hospital admissions during neoadjuvant chemotherapy	Measured in percentage	Baseline to time of breast surgery estimated up to 30 weeks
Secondary	Total length of hospital admissions during neoadjuvant chemotherapy	Measured in days	Baseline to time of breast surgery estimated up to 30 weeks
Secondary	Changes in total body mass	Changes from baseline measured by bioelectrical impedance analysis.	Baseline, during the week before breast surgery, 3 months after breast surgery
Secondary	Changes in lean body mass	Changes from baseline measured by bioelectrical impedance analysis.	Baseline, during the week before breast surgery, 3 months after breast surgery
Secondary	Changes in fat mass	Changes from baseline measured by bioelectrical impedance analysis.	Baseline, during the week before breast surgery, 3 months after breast surgery
Secondary	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).	Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
Secondary	Changes in muscle strength	Changes in 1 repetition maximum strength from baseline measured on leg press and pull down.	Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
Secondary	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.	Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
Secondary	Changes in level of physical activity	Changes in activity data measured by a wearable objective measurement device.	Baseline, during the week before breast surgery, 3 months after breast surgery
Secondary	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).	Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
Secondary	Changes in general anxiety	Changes in self-reported general anxiety from baseline assessed on the Generalised Anxiety Disorder 7-item (GAD-7).	Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
Secondary	Changes in depression	Changes in self-reported depression from baseline assessed on the Patient Health Questionnaire-9 (PHQ-9).	Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
Secondary	Changes in psychological distress	Changes in self-reported psychological distress from baseline assessed on the Distress Thermometer (DT).	Baseline, week 13 during neoadjuvant chemotherapy, during the week before breast surgery, 3 months after breast surgery
Secondary	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.	Breast surgery to 3 months after breast surgery
Secondary	Tumour size	Assessed by doctors' clinical examination of the breast.	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
Secondary	Tumour size	Measured by a pathologist from the tumour surgical specimen at breast surgery.	At time of breast surgery estimated to take place within 30 weeks from baseline
Secondary	Pathological response grade	Assessed by a pathologist from the tumour surgical specimen at breast surgery.	At time of breast surgery estimated to take place within 30 weeks from baseline
Secondary	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.	Baseline (pre-chemotherapy) to time of breast surgery estimated up to 30 weeks
Secondary	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.	Baseline (pre-chemotherapy) to time of breast surgery estimated up to 30 weeks
Secondary	Liquid biopsies	Changes in cell free DNA from blood samples. Furthermore, circulating tumour DNA will be investigated if possible.	Baseline, approximately week 7, 13 and 19, 3 months after breast surgery
Secondary	Metabolic and inflammatory markers	Changes in glucose, hba1c, zinc, magnesium, phosphate and C reactive protein (CRP) levels from blood samples.	Baseline, approximately week 13 and 19, 3 months after breast surgery
Secondary	Cytokines	Changes in cytokines from blood samples before, during and after neoadjuvant chemotherapy.	Baseline, approximately week 13 and 19, 3 months after breast surgery
Secondary	Cell proliferation	In vitro cell proliferation response with sera collected from blood samples before and after exercise.	Approximately between week 1-4 during neoadjuvant chemotherapy and within 6 weeks before breast surgery
Secondary	Recurrence	Incidence of breast cancer recurrence in percent	Breast surgery to up to 10 years follow-up after breast surgery
Secondary	Survival	Risk of mortality	Breast surgery to up to 10 years follow-up after breast surgery