Breast Cancer
Conditions
Keywords
cardiac toxicities
Brief summary
Several large adjuvant trastuzumab trials have demonstrated improved overall survival in participants with early stage breast cancer, with a 33% decrease in risk of death. However, retrospective analyses of participant outcomes in these trials have demonstrated increased risk of cardiotoxicity (i.e damage to the heart) in a small number of patients (4-8%). At this time, investigators are unable to predict which participants are at increased risk of cardiac-related treatment complications. Currently all patients receive regular cardiac imaging throughout their one year of trastuzumab treatment. At this time, the optimal monitoring schedule for trastuzumab-related cardiotoxicity remains unknown, and several published consensus guidelines are currently in use as standard of care.
Interventions
PROCEDURELVEF 3 month
cardiac evaluation (by either transthoracic echocardiography or MUGA) every 3 months
PROCEDURELVEF 4 month
cardiac evaluation (by either transthoracic echocardiography or MUGA) every 4 months
Sponsors
Ottawa Hospital Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed early stage HER2-positive breast cancer * Planned trastuzumab therapy for early stage breast cancer * ≥18 years of age * Able to provide verbal consent * Normal LVEF (\>53%) before trastuzumab therapy
Exclusion criteria
• Contraindication to transthoracic echocardiography or MUGA
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LVEF Results | Baseline to 1 year | Changes in Left Ventricular Ejection Fraction (LVEF) results compared to baseline (by echocardiography or MUGA) throughout the course of trastuzumab based therapy. LVEF is measured as a percentage. The outcome is a change in LVEF percentage (%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Trastuzumab Delay and Discontinuation | 1 year | The number of participants who had a delay and/or discontinuation in trastuzumab treatment. Data was collected from physicians following clinic visits and from patient electronic medical records. |
| Referral to Cardiology | 1 year | The number of participants who were referred to cardiology. Data was collected from physicians following clinic visits, and from the patient's electronic medical record. |
| Rate of Cardiac Events | 1 year | The number of participants who experienced a decrease in ejection fraction (EF), congestive heart failure, or other cardiac events within the 1 year of study. Examples of other cardiac events include change in blood pressure, chest pain/shortness of breath, or irregular heartbeat. Data was collected/reported from physicians following clinic appointments, and from the patient's electronic medical record. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LVEF 3 Month cardiac evaluation (by either transthoracic echocardiography or MUGA) every 3 months
LVEF 3 month: cardiac evaluation (by either transthoracic echocardiography or MUGA) every 3 months | 98 |
| LVEF 4 Month cardiac evaluation (by either transthoracic echocardiography or MUGA) every 4 months
LVEF 4 month: cardiac evaluation (by either transthoracic echocardiography or MUGA) every 4 months | 97 |
| Total | 195 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Completed Study as Planned | Location | 1 | 1 |
| Completed Study as Planned | Metastatic disease | 3 | 0 |
| Completed Study as Planned | Protocol Violation | 2 | 6 |
| Completed Study as Planned | Reason = LVEF | 2 | 2 |
| Per Protocol Population | Participant Decision | 0 | 2 |
| Per Protocol Population | Physician Decision | 2 | 1 |
Baseline characteristics
| Characteristic | LVEF 3 Month | LVEF 4 Month | Total |
|---|---|---|---|
| Age, Continuous | 55.4 years STANDARD_DEVIATION 11.4 | 54.8 years STANDARD_DEVIATION 11.3 | 55.1 years STANDARD_DEVIATION 11.4 |
| Anthracycline-based chemotherapy | 53 Participants | 50 Participants | 103 Participants |
| Baseline Left Ventricular Ejection Fraction (LVEF) | 65 LVEF Percentage (%) | 64 LVEF Percentage (%) | 65 LVEF Percentage (%) |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 98 Participants | 97 Participants | 195 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 98 | 0 / 97 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
LVEF Results
Changes in Left Ventricular Ejection Fraction (LVEF) results compared to baseline (by echocardiography or MUGA) throughout the course of trastuzumab based therapy. LVEF is measured as a percentage. The outcome is a change in LVEF percentage (%).
Time frame: Baseline to 1 year
Population: Per Protocol Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LVEF 3 Month | LVEF Results | -8 LVEF Percentage (%) |
| LVEF 4 Month | LVEF Results | -6 LVEF Percentage (%) |
95% CI: [-2.5, 1.2]
Secondary
Rate of Cardiac Events
The number of participants who experienced a decrease in ejection fraction (EF), congestive heart failure, or other cardiac events within the 1 year of study. Examples of other cardiac events include change in blood pressure, chest pain/shortness of breath, or irregular heartbeat. Data was collected/reported from physicians following clinic appointments, and from the patient's electronic medical record.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LVEF 3 Month | Rate of Cardiac Events | 31 Participants |
| LVEF 4 Month | Rate of Cardiac Events | 24 Participants |
Secondary
Rates of Trastuzumab Delay and Discontinuation
The number of participants who had a delay and/or discontinuation in trastuzumab treatment. Data was collected from physicians following clinic visits and from patient electronic medical records.
Time frame: 1 year
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LVEF 3 Month | Rates of Trastuzumab Delay and Discontinuation | Delay | 9 Participants |
| LVEF 3 Month | Rates of Trastuzumab Delay and Discontinuation | Discontinuation | 2 Participants |
| LVEF 4 Month | Rates of Trastuzumab Delay and Discontinuation | Delay | 2 Participants |
| LVEF 4 Month | Rates of Trastuzumab Delay and Discontinuation | Discontinuation | 7 Participants |
Secondary
Referral to Cardiology
The number of participants who were referred to cardiology. Data was collected from physicians following clinic visits, and from the patient's electronic medical record.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LVEF 3 Month | Referral to Cardiology | 12 Participants |
| LVEF 4 Month | Referral to Cardiology | 12 Participants |