Cancer, BreastEXACT2NCT03748550
Exercise to Prevent AnthraCycline-based Cardio-Toxicity Study 2.0 (EXACT2)
A study testing Aerobic exercise in people with Cancer, Breast and Cardiotoxicity, run by Nova Scotia Health Authority at 2 sites in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cancer, Breast, Cardiotoxicity, Cardiovascular Diseases
- What is being tested?
- Aerobic exercise
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 2 sitesCanada
- Study dates
- 29 Apr 2019to 31 Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1) must be 18 years or older.
- diagnosed with breast cancer (stages I-III) and not have started therapy.
- must be scheduled to receive AC- based chemotherapy (minimum dose of 240 mg/m2 of DOX or 300 mg/m2 of DAN).
- are able to undertake a 12-week home-based, progressive aerobic exercise program.
- have medical clearance from a cardiologist (e.g. based on stress test results) to participate in the study.
Who cannot join
- significant cognitive limitations.
- pre-existing medical condition that would otherwise contraindicate aerobic exercise.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
QEII Health Sciences Centre
Halifax, Nova Scotia, B3H 1V8
St. Boniface Hospital
Winnipeg, Manitoba, R2H 2A6
About this study
Official title: EXercise to Prevent AnthraCycline-based Cardio-Toxicity 2.0 (EXACT2) in Individuals With Breast Cancer
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.
Read the detailed description
As a result of advances in cancer treatment, the number of breast cancer (BC) survivors is increasing in Canada. Unfortunately, the drugs used to treat BC can have a negative impact on the long term health and welfare of the BC survivors (BCS). For example, commonly used cancer therapies, such as anthracyclines (AC) are known to cause declines in heart health. While the impact can vary, some individuals treated with these medications will experience substantial heart damage that may lead to heart failure and death. As a result, risk of cardiovascular morbidity/mortality has become a major concern for BCS that received AC treatment. As a result, there is an immediate need to find therapies that can be used to prevent damage to the heart without limiting the anticancer potential of AC.
A growing body of evidence suggests that aerobic exercise training may help protect the heart against the damaging effects of AC therapy. These studies, which were conducted using animal models, have shown that performing aerobic exercise before or while undergoing AC therapy helps to maintain heart function and prevent structural changes in the heart. However, to the author's knowledge similar studies have not been conducted in BCS undergoing treatment, thus it remains unclear whether exercise has the same cardioprotective effect in BCS. As a first step in answering this question, our research group conducted a pilot study that showed a 12-week aerobic exercise program is safe and feasible for BCS undergoing chemotherapy. The next step in our research is to determine whether aerobic exercise decreases or prevents cardiotoxicity in BCS receiving AC treatment. Therefore, the purpose of this study is to determine whether a 12-week home based aerobic exercise program mitigates AC-mediated cardiotoxicity in BCS on active treatment. The specific objectives of the study are to determine whether the aerobic exercise program: 1) prevents structural and functional changes in the heart; 2) maintains peak aerobic capacity throughout the treatment process; and 3) decreases biological markers associated with heart damage.
This is a randomized control trial with repeated measures. BCSs will be randomly assigned to either the wait-list control (CTL) group (standard of care (SOC) or the aerobic exercise (AEX; SOC + 12-week home-based aerobic exercise program). One hundred BCS (18-65 years of age) on AC treatment will be recruited from two sites, Halifax, NS (n=50) and Winnipeg, MB (n=50). Patients in the AEX group will perform two exercise sessions per week that will range from low intensity (~45 min) to vigorous intensity (~20 min). BCS will monitor their exercise intensity with Polar A370 HR monitors, which they will be given for the duration of the study.The primary outcome measure for the study is cardiac function as determined by echocardiography and a cardiac stress test. Secondary outcome measures include serum biomarkers associated with cardiotoxicity (e.g. c-reactive protein, hsTNT, NT-proBNP). Patient-reported outcomes including levels of fatigue and quality of life will also be assessed. The study outcome measures will be assessed prior to the participants starting AC therapy (week-0), post-exercise intervention (week-12) and 6 months after the completion of the AEX. Of note, upon completion of the 6 month follow-up testing participants in the CTL group, if interested, will be given the home-based AEX as well the necessary support to complete the program.
This research will provide the first direct evidence that aerobic exercise protects the heart from AC-mediated damage in BCS undergoing cancer treatment. Both the medical and research communities will benefit from this research as it could lead to the improvement of long term health of cancer survivorship as well as improve the understanding of how the heart health can be maintained during cancer therapy. Given the significant impact of AC therapy on improving BC prognosis, and the potential protective effects of exercise training, this study will be important in improving BC care via the improvement of the quality of life and increased survivorship.
- Conditions
- Cancer, Breast, Cardiotoxicity, Cardiovascular Diseases
- Being tested
- Aerobic exercise
- Keywords
- Anthracyclines, Cardiotoxic, Breast cancer, Aerobic exercise, Cardiac structure, Cardiac function, CVD risk
- Medical subject headings
- Breast Neoplasms, Cardiotoxicity, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aerobic exerciseBehavioural
All participants will receive standard of care for their cancer as well as given a 12-week, home-based progressive aerobic exercise (AE) program. A nonlinear progressive training approach will be used whereby each participant will perform two AE sessions (e.g. walking), on non-consecutive days, per week. AE sessions will vary between low (35-45% heart rate reserve (HRR)), low-moderate (46-55% HRR), high-moderate (56-70% HRR) and high (71-85% HRR) intensity.
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | Participants will receive standard of care treatment for their breast cancer. |
| Exercise | Experimental | Participants will receive standard of care treatment for their breast cancer plus be given a 12-week home based aerobic exercise program. Receives: Behavioral: Aerobic exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Left Ventricular (LV) Function
LV function will be assessed using serial transthoracic echocardiography (TTE) as well as tissue velocity imaging (TVI) and strain imaging (SI.) For 2-dimensional (2D) LV cavity dimensions and LVEF will be determined from the acquired 2D images according to established criteria. Tissue Doppler-derived indexes will be recorded at the base of the lateral mitral annuli to determine longitudinal endocardial velocities. The indexes that will be assessed are systolic (S'), early diastolic (e') and late diastolic (a') velocities. Doppler-independent strain will be assessed offline using semi-automated speckle tracking techniques. These will be performed using parasternal and apical views to determine both global longitudinal and radial strain.
Measured: LV function will be assessed at baseline (week 0), post-intervention (week-13) and 6 months after the completion of the intervention.
Secondary outcomes (5)
Change in Cardiac Electrical Activity
Cardiac electrocardiogram at rest will be assessed using a 12 lead ECG (General Electric Case System). Specifically, the duration (ms) of the PR interval, RR interval, QRS interval and QT interval will be determined.
Measured: The cardiac ECG will be assessed at baseline (week 0), post-intervention (week-13) and 6 months after the completion of the intervention.
Change in Aerobic Fitness
Cardiac Stress Tests results will be used to predict peak oxygen consumption (ml/kg/min). In brief, participants will perform a graded exercise test until they reach volitional fatigue or the test is terminated due to adverse physiological changes. Predictive equations will then be used to predict the participant's peak oxygen uptake based on the total duration (seconds) of the treadmill test.
Measured: Outcome will be assessed at baseline (week 0), post-intervention (week-13) and 6 months after the completion of the intervention.
Change in Blood biomarkers
Venipuncture will be performed by a nurse/phlebotomist to collect blood samples which will be used to quantify systemic levels of c-reactive protein (CRP), high sensitivity troponin (hs-TNT) and NTproBNP levels. Upon collection, blood samples will be processed, and the serum will be extracted and stored at -20°C until it is required for analysis. CRP, hs-TNT and N-terminal pro b-type natriuretic peptide (NTproBNP) levels will be assessed using commercially available ELISA kits. All biomarkers will be measured in pg/ml.
Measured: Outcome will be assessed at baseline (week 0), post-intervention (week-13) and 6 months after the completion of the intervention.
Change in Functional Assessment for Cancer Therapy
The Functional Assessment for Cancer Therapy survey for patients with breast cancer (FACT-B) will be used to assess quality of life. The FACT-B includes sub-scales for assessing physical, social/family, emotional, and functional well-being. FACT-B total score ranges from 0-148.
Measured: Outcome will be assessed at baseline (week 0), post-intervention (week-13) and 6 months after the completion of the intervention.
Change in Fatigue
The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) is a 13 item questionnaire (maximum score =160) that will be used to assess cancer-related fatigue. Higher scores are indicative of higher levels of fatigue.
Measured: Outcome will be assessed at baseline (week 0), post-intervention (week-13) and 6 months after the completion of the intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2018
- Study start29 Apr 2019
- Primary completion30 Jun 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cancer, BreastStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomly allocated to either the standard of care group (control) or the intervention group (standard of care + 12-weeks aerobic exercise).
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nova Scotia Health Authority
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Cancer Society (CCS), Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03748550
- Sponsor's protocol ID
- 1024489
- Other IDs
- 1024489
- Acronym
- EXACT2
- Status last verified
- Aug 2024
- First submitted
- 13 Nov 2018
- Last updated
- 21 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- EXercise to Prevent AnthraCycline-based Cardio-Toxicity 2.0 (EXACT2) in Individuals With Breast Cancer
- ClinicalTrials.gov ID
- NCT03748550
- Acronym / sponsor ID
- EXACT2 / 1024489
- Conditions
- Cancer, Breast, Cardiotoxicity, Cardiovascular Diseases
- Keywords
- Anthracyclines, Cardiotoxic, Breast cancer, Aerobic exercise, Cardiac structure, Cardiac function, CVD risk
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Nova Scotia Health AuthorityUniversity, hospital or other
- Collaborators
- Canadian Cancer Society (CCS), Canadian Institutes of Health Research (CIHR)
- Study start
- 29 Apr 2019 (actual)
- Primary completion
- 30 Jun 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 21 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
As a result of advances in cancer treatment, the number of breast cancer (BC) survivors is increasing in Canada. Unfortunately, the drugs used to treat BC can have a negative impact on the long term health and welfare of the BC survivors (BCS). For example, commonly used cancer therapies, such as anthracyclines (AC) are known to cause declines in heart health. While the impact can vary, some individuals treated with these medications will experience substantial heart damage that may lead to heart failure and death. As a result, risk of cardiovascular morbidity/mortality has become a major concern for BCS that received AC treatment. As a result, there is an immediate need to find therapies that can be used to prevent damage to the heart without limiting the anticancer potential of AC.
A growing body of evidence suggests that aerobic exercise training may help protect the heart against the damaging effects of AC therapy. These studies, which were conducted using animal models, have shown that performing aerobic exercise before or while undergoing AC therapy helps to maintain heart function and prevent structural changes in the heart. However, to the author's knowledge similar studies have not been conducted in BCS undergoing treatment, thus it remains unclear whether exercise has the same cardioprotective effect in BCS. As a first step in answering this question, our research group conducted a pilot study that showed a 12-week aerobic exercise program is safe and feasible for BCS undergoing chemotherapy. The next step in our research is to determine whether aerobic exercise decreases or prevents cardiotoxicity in BCS receiving AC treatment. Therefore, the purpose of this study is to determine whether a 12-week home based aerobic exercise program mitigates AC-mediated cardiotoxicity in BCS on active treatment. The specific objectives of the study are to determine whether the aerobic exercise program: 1) prevents structural and functional changes in the heart; 2) maintains peak aerobic capacity throughout the treatment process; and 3) decreases biological markers associated with heart damage.
This is a randomized control trial with repeated measures. BCSs will be randomly assigned to either the wait-list control (CTL) group (standard of care (SOC) or the aerobic exercise (AEX; SOC + 12-week home-based aerobic exercise program). One hundred BCS (18-65 years of age) on AC treatment will be recruited from two sites, Halifax, NS (n=50) and Winnipeg, MB (n=50). Patients in the AEX group will perform two exercise sessions per week that will range from low intensity (~45 min) to vigorous intensity (~20 min). BCS will monitor their exercise intensity with Polar A370 HR monitors, which they will be given for the duration of the study.The primary outcome measure for the study is cardiac function as determined by echocardiography and a cardiac stress test. Secondary outcome measures include serum biomarkers associated with cardiotoxicity (e.g. c-reactive protein, hsTNT, NT-proBNP). Patient-reported outcomes including levels of fatigue and quality of life will also be assessed. The study outcome measures will be assessed prior to the participants starting AC therapy (week-0), post-exercise intervention (week-12) and 6 months after the completion of the AEX. Of note, upon completion of the 6 month follow-up testing participants in the CTL group, if interested, will be given the home-based AEX as well the necessary support to complete the program.
This research will provide the first direct evidence that aerobic exercise protects the heart from AC-mediated damage in BCS undergoing cancer treatment. Both the medical and research communities will benefit from this research as it could lead to the improvement of long term health of cancer survivorship as well as improve the understanding of how the heart health can be maintained during cancer therapy. Given the significant impact of AC therapy on improving BC prognosis, and the potential protective effects of exercise training, this study will be important in improving BC care via the improvement of the quality of life and increased survivorship.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomly allocated to either the standard of care group (control) or the intervention group (standard of care + 12-weeks aerobic exercise).
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –Participants will receive standard of care treatment for their breast cancer. |
| Exercise | Experimental | Behavioral: Aerobic exerciseParticipants will receive standard of care treatment for their breast cancer plus be given a 12-week home based aerobic exercise program. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 1) must be 18 years or older.
- diagnosed with breast cancer (stages I-III) and not have started therapy.
- must be scheduled to receive AC- based chemotherapy (minimum dose of 240 mg/m2 of DOX or 300 mg/m2 of DAN).
- are able to undertake a 12-week home-based, progressive aerobic exercise program.
- have medical clearance from a cardiologist (e.g. based on stress test results) to participate in the study.
Key exclusion criteria (2 listed)
- significant cognitive limitations.
- pre-existing medical condition that would otherwise contraindicate aerobic exercise.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aerobic exerciseAll participants will receive standard of care for their cancer as well as given a 12-week, home-based progressive aerobic exercise (AE) program. A nonlinear progressive training approach will be used whereby each participant will perform two AE sessions (e.g. walking), on non-consecutive days, per week. AE sessions will vary between low (35-45% heart rate reserve (HRR)), low-moderate (46-55% HRR), high-moderate (56-70% HRR) and high (71-85% HRR) intensity. | Behavioural | Exercise |
Primary outcome
Change in Left Ventricular (LV) Function
Time frame: LV function will be assessed at baseline (week 0), post-intervention (week-13) and 6 months after the completion of the intervention.
LV function will be assessed using serial transthoracic echocardiography (TTE) as well as tissue velocity imaging (TVI) and strain imaging (SI.) For 2-dimensional (2D) LV cavity dimensions and LVEF will be determined from the acquired 2D images according to established criteria. Tissue Doppler-derived indexes will be recorded at the base of the lateral mitral annuli to determine longitudinal endocardial velocities. The indexes that will be assessed are systolic (S'), early diastolic (e') and late diastolic (a') velocities. Doppler-independent strain will be assessed offline using semi-automated speckle tracking techniques. These will be performed using parasternal and apical views to determine both global longitudinal and radial strain.
5 secondary outcomes
Change in Cardiac Electrical Activity
Time frame: The cardiac ECG will be assessed at baseline (week 0), post-intervention (week-13) and 6 months after the completion of the intervention.
Change in Aerobic Fitness
Time frame: Outcome will be assessed at baseline (week 0), post-intervention (week-13) and 6 months after the completion of the intervention.
Change in Blood biomarkers
Time frame: Outcome will be assessed at baseline (week 0), post-intervention (week-13) and 6 months after the completion of the intervention.
Change in Functional Assessment for Cancer Therapy
Time frame: Outcome will be assessed at baseline (week 0), post-intervention (week-13) and 6 months after the completion of the intervention.
Change in Fatigue
Time frame: Outcome will be assessed at baseline (week 0), post-intervention (week-13) and 6 months after the completion of the intervention.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2024.
- Individual participant dataSharing planned: No
Related trials for Cancer, Breast
Not yet recruiting
Decision Support for Chemoprevention
Breast Cancer
Active, not recruiting
Improving Patient-Centered Communication in Breast Cancer Through Patient and Provider Interventions
Anatomic Stage 0 Breast Cancer AJCC v8, Anatomic Stage I Breast Cancer AJCC v8
Not yet recruitingPhase 2
The Impact of Using Nicorandil for the Prevention of Doxorubicin-Induced Cardiotoxicity
Doxorubicin Induced Cardiotoxicity, Doxorubicin Induced Cardiomyopathy
Not yet recruiting
Tolerability of Dalpiciclib vs. Abemaciclib/Ribociclib in Early HR+/HER2- Breast Cancer
Breast Cancer
Active, not recruitingObservational study
Assessment of Cognitive Function in Breast Cancer and Lymphoma Patients Receiving Chemotherapy
Breast Cancer, Lymphoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Aerobic exercise in people with Cancer, Breast and Cardiotoxicity, run by Nova Scotia Health Authority at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Left Ventricular (LV) Function (time frame: LV function will be assessed at baseline (week 0), post-intervention (week-13) and 6 months after the completion of the intervention.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2024.