Aerobic Exercise for Cardiovascular Protection in Breast Cancer Patients

(EXACT2 Trial)

Recruiting at 1 trial location

Overseen By Melanie R Keats, PhD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Nova Scotia Health Authority

Must be taking: AC-based chemotherapy

Disqualifiers: Cognitive limitations, contraindicate aerobic exercise

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

7 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Aerobic Exercise for Cardiovascular Protection in Breast Cancer Patients?

Research shows that aerobic exercise can significantly improve heart and lung function in women with breast cancer and help reduce the harmful side effects of chemotherapy. It also appears to protect against heart damage caused by cancer treatments. ^{1 2 3 4 5}

Is aerobic exercise safe for breast cancer patients?

Research shows that aerobic exercise is generally safe for breast cancer patients and can help reduce heart-related side effects of cancer treatments. ^{2 4 5 6 7}

How is aerobic exercise different from other treatments for breast cancer patients?

Aerobic exercise is unique because it helps protect the heart from damage caused by breast cancer treatments, improving heart and lung function without the use of medication. Unlike traditional treatments, it focuses on physical activity to enhance overall cardiovascular health. ^{1 4 5 8 9}

What is the purpose of this trial?

Although great progress has been made in treating breast cancer, long-term health may be impaired by cancer therapy. For example, some chemotherapy drugs (e.g., anthracyclines) are known to cause declines in heart health. While the impact can vary, some will experience substantial heart damage that may lead to heart failure and death. As these treatments are highly effective, there is a need to find ways to reduce the damaging effects while not interfering with its anticancer potential. As it is well-known that regular exercise can improve heart health, the purpose of this study is to explore the role of exercise as a heart protective therapy for breast cancer patients receiving heart damaging chemotherapy.

Eligibility Criteria

The EXACT2 trial is for adults over 18 with stages I-III breast cancer who are about to start chemotherapy that can harm the heart. Participants must be cleared by a cardiologist and able to do a 12-week home-based aerobic exercise program. It's not for those with cognitive issues or conditions that make exercise unsafe.

Inclusion Criteria

have medical clearance from a cardiologist (e.g. based on stress test results) to participate in the study.

You must be set to get a specific type of chemotherapy called AC-based chemotherapy with a certain minimum dose.

You can do a 12-week exercise program at home that gradually gets more challenging.

Exclusion Criteria

You have major problems with thinking and understanding.

You have a medical condition that would make it unsafe for you to do aerobic exercise.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anthracycline-based chemotherapy and are randomly assigned to either a control group or an exercise group with a 12-week home-based aerobic exercise program

12 weeks

Weekly monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cardiac function and quality of life assessments

6 months

3 visits (in-person)

Open-label extension (optional)

Participants in the control group may opt into the home-based aerobic exercise program after the follow-up period

12 weeks

Treatment Details

Interventions

• Aerobic exercise

Trial Overview This study tests if regular aerobic exercise can protect the hearts of breast cancer patients from damage caused by anthracycline-based chemotherapy, which is known to potentially lead to heart failure.

Participant Groups

Group I: Exercise Experimental Treatment 1 Intervention

Participants will receive standard of care treatment for their breast cancer plus be given a 12-week home based aerobic exercise program.

Group II: Control Active Control 1 Intervention

Participants will receive standard of care treatment for their breast cancer.

Aerobic exercise is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Aerobic Exercise for:

• Rehabilitation after stroke
• Improvement of physical function
• Enhancement of cognitive function
• Reduction of depression

Approved in European Union as Aerobic Exercise for:

• Cardiovascular rehabilitation
• Improvement of physical function
• Enhancement of cognitive function

Approved in Canada as Aerobic Exercise for:

• Rehabilitation after stroke
• Improvement of physical function
• Enhancement of cognitive function

Who Is Running the Clinical Trial?

Nova Scotia Health Authority

Lead Sponsor

Trials

302

Recruited

95,300+

Canadian Cancer Society (CCS)

Collaborator

Trials

84

Recruited

42,100+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Findings from Research

Aerobic exercise training (AET) combined with neoadjuvant chemotherapy (doxorubicin-cyclophosphamide) significantly improved exercise capacity and vascular function in 20 women with early breast cancer, suggesting a beneficial interaction between AET and chemotherapy.

The AET group showed a notable 38% reduction in tumor blood flow, along with changes in circulating factors related to angiogenesis, indicating that AET may influence tumor biology during chemotherapy, although no differences were found in tumor tissue markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of circulating angiogenic factors and tumor biology by aerobic training in breast cancer patients receiving neoadjuvant chemotherapy. Jones, LW., Fels, DR., West, M., et al.[2021]

In a study of 20 breast cancer patients undergoing neoadjuvant chemotherapy, those who participated in moderate-to-high intensity aerobic training showed a significant improvement in cardiopulmonary function, with a 13.3% increase in VO2peak compared to a decrease in the control group.

The aerobic training was found to be safe, with only one adverse event reported during the training sessions, and no significant differences in treatment-related side effects between the groups, indicating that it can be a beneficial adjunct therapy during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of aerobic training in operable breast cancer patients receiving neoadjuvant chemotherapy: a phase II randomized trial. Hornsby, WE., Douglas, PS., West, MJ., et al.[2022]

Aerobic exercise significantly improves cardiorespiratory fitness (CRF) in breast cancer patients undergoing treatments that may cause cardiotoxicity, with a strong effect size (SMD 1.79) based on a review of 16 trials involving 876 participants.

Exercise regimens that include moderate to vigorous intensity, performed up to three times a week for more than 30 minutes, are particularly effective in enhancing CRF during breast cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Aerobic Exercise Training to Mitigate Cardiotoxicity of Breast Cancer Therapy: A Systematic Review and Meta-Analysis. Tsai, YL., Chuang, YC., Chen, CP., et al.[2023]

A meta-analysis of 11 randomized controlled trials involving 666 breast cancer patients found that physical exercise significantly improves cardiovascular health by lowering systolic and diastolic blood pressure, triglyceride levels, and body mass index.

Exercise also enhances cardiovascular fitness by increasing peak oxygen uptake and high-density lipoprotein cholesterol levels, suggesting it could be an effective intervention for cardiovascular care in breast cancer recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of physical exercise on the cardiovascular system in breast cancer patients: a systematic review and meta-analysis of randomized controlled trials. Wang, S., Yang, T., Qiang, W., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

A meta-analysis of aerobic exercise interventions for women with breast cancer. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Modulation of circulating angiogenic factors and tumor biology by aerobic training in breast cancer patients receiving neoadjuvant chemotherapy. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of aerobic training in operable breast cancer patients receiving neoadjuvant chemotherapy: a phase II randomized trial. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Feasibility of Aerobic Exercise Training to Mitigate Cardiotoxicity of Breast Cancer Therapy: A Systematic Review and Meta-Analysis. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Effect of aerobic exercise on cardiotoxic outcomes in women with breast cancer undergoing anthracycline or trastuzumab treatment: a systematic review and meta-analysis. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Exercise improves body fat, lean mass, and bone mass in breast cancer survivors. [2023]

7. Pakistan pubmed.ncbi.nlm.nih.gov

Effect of anthracycline combined with aerobic exercise on the treatment of breast cancer. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Effectiveness of physical exercise on the cardiovascular system in breast cancer patients: a systematic review and meta-analysis of randomized controlled trials. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Cardiopulmonary responses and adherence to exercise in women newly diagnosed with breast cancer undergoing adjuvant therapy. [2022]