Breast Cancer
Conditions
Brief summary
The overall of this proposal is to test in community hospitals the utility of a 10-min magnetic resonance imaging (MRI) scan protocol combined with proprietary image analysis algorithms for detecting early cardiovascular (CV) injury during receipt of chemotherapy for breast cancer (BrC) and lymphoma. This technology provides health-care delivery systems with a time-efficient method to identify those at risk of a future CV event so that prevention can be implemented to prolong survival and reduce morbidity in cancer survivors.
Detailed description
While recent research indicates that conventional MRI, advanced echocardiography (global longitudinal strain and 3D) and serum biomarkers can detect CV injury early after receipt of Chemotherapy, these methods require lengthy and difficult examinations that are not routinely executed in community hospitals where the majority of patients with BrC & lymphoma are treated. Yet, 1-month deteriorations in traditional 45-min MRI measures are known to forecast 6-month subclinical deteriorations in left ventricular ejection fraction (LVEF) that are associated with CV events. At the same time, new observational data indicate therapy with HMG-CoA reductase inhibitors/statins administered early during receipt of Chemotherapy may prevent subsequent cardiac dysfunction and CV events. Our MRI fast scanning techniques remedy these community hospital implementation obstacles. In this proposal, the investigators propose to test the utility of these fast scans within an existing funded randomized clinical trial R01HL118740 of generic atorvastatin that is researching methods to prevent cardiotoxicity in patients treated with Chemotherapy for BrC and lymphoma (taking advantage of significant existing clinical trial resources). This study allows us to address our over-arching goal: to determine the optimal implementation (alone or in combination with other tests) of our proprietary MRI processes for forecasting CV injury in patients treated with Chemotherapy in community hospitals through performance of a Phase II comparative effectiveness study within an ongoing clinical trial.
Interventions
DIAGNOSTIC_TESTFast MRI
The fast MRI is a 10 minute MRI scan that will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment.
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed Stage I-III breast cancer (including inflammatory and newly diagnosed recurrent breast cancer) or lymphoma with a \> 2 year life expectancy * Scheduled to receive chemotherapy with an Anthracycline (doxorubicin or epirubicin) * = or \> 21 years of age * Prior cancers allowed if no evidence of disease * ECOG 0 or 1 * Enrollment in NCI Protocol #: WF 98213. Patients must receive Fast MRI and 3D ECHO along with Baseline (98213) MRI prior to first chemotherapy treatment.
Exclusion criteria
* Patients with ferromagnetic cerebral aneurysm clips or other intraorbital/intracranial metal; pacemakers, defibrillators, functioning neurostimulator devices or other implanted electronic devices. * Most breast tissue expanders are not allowed. (If uncertain, inform the MRI tech to confirm eligibility status.) * Unable to provide informed consent * Symptomatic Claustrophobia * Pregnant or breasting feeding. Due to unknown risks and potential harm to the unborn fetus a negative serum pregnancy test within 10 days prior to registration is required in patients with child-bearing potential. For this reason patients of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence (not having sex), oral contraceptives, intrauterine device (IUD), DeProvera, tubal ligation, or vasectomy of the partner (with confirmed negative sperm counts) in a monogamous relationship (same partner). An acceptable, although less reliable method involves the careful use of condoms and spermicidal foam or gel and/or cervical cap or sponge prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pulse Wave Velocity (PWV) at Baseline and 6 Months | Baseline and 6 months | To compare baseline and 6 month measures in pulse wave velocity (PWV) |
| Left Ventricular Ejection Fraction (LVEF) at Baseline, 2 Month Using Fast MRI, and 6 Months | Baseline, 2 months, and 6 months | To compare baseline, 2-month (using Fast MRI), and 6 month measures in left ventricular (LV) ejection fraction |
| End Diastolic Volume (EDV) at Baseline, 2 Month, and 6 Months | Baseline, 2 months, and 6 months | To compare baseline, 2-month (using Fast MRI), and 6 month measures in end Diastolic Volume (EDV) |
| End Systolic Volume (ESV) at Baseline, 2 Month, and 6 Months | Baseline, 2 months, and 6 months | To compare baseline, 2-month (using Fast MRI), and 6 month measures in end Systolic Volume (ESV) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Ejection Fraction (LVEF): Comparison of Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline | Baseline | To compare Magnetic Resonance Imaging (MRI) metric of Left Ventricular Ejection Fraction (LVEF) with Echocardiogram (ECHO) at baseline |
| End Diastolic Volume (EDV): Compare Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline | Baseline | To compare magnetic resonance imaging (MRI) metric of End Diastolic Volume (EDV) with echocardiogram (ECHO) at baseline |
| End Systolic Volume (ESV): Compare Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline | Baseline | To compare magnetic resonance imaging (MRI) metric of End Systolic Volume (ESV) with echocardiogram (ECHO) at baseline |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Algorithmic Modeling | Baseline to 6 months | To use exploratory algorithmic modeling to obtain optimal strategies for determining the combination of metrics (10-min MR, ECHO, serum biomarkers) at 2-months that predict the 6-month post Chemotherapy deteriorations in cardiovascular function. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fast MRI All patients who agree to participate in this study will have a 10 minute fast MRI scan and Baseline and 6 month time periods. The fast MRI will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment.
Fast MRI: The fast MRI is a 10 minute MRI scan that will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment. | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Fast MRI |
|---|---|
| Age, Continuous | 45.1 years STANDARD_DEVIATION 15.3 |
| End Diastolic Volume (EDV) - Echocardiogram (ECHO) | 100.08 mL STANDARD_DEVIATION 24.2 |
| End Diastolic Volume (EDV) - Magnetic Resonance Imaging (MRI) | 134.90 mL STANDARD_DEVIATION 41.7 |
| End Systolic Volume (ESV) - Echocardiogram (ECHO) | 44.90 mL STANDARD_DEVIATION 9.16 |
| End Systolic Volume (ESV) - Magnetic Resonance Imaging (MRI) | 52.23 mL STANDARD_DEVIATION 18.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Left Ventricular Ejection Fraction (LVEF) | 61.51 percentage of fluid expelled STANDARD_DEVIATION 5.45 |
| Left Ventricular Ejection Fraction (LVEF) - Echocardiogram (ECHO) | 54.17 percentage of fluid expelled STANDARD_DEVIATION 7.03 |
| Pulse Wave Velocity (PWV) - Magnetic Resonance Imaging (MRI) | 4.74 meters/sec STANDARD_DEVIATION 1.75 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
End Diastolic Volume (EDV) at Baseline, 2 Month, and 6 Months
To compare baseline, 2-month (using Fast MRI), and 6 month measures in end Diastolic Volume (EDV)
Time frame: Baseline, 2 months, and 6 months
Population: Only 5 received MRI at baseline, 4 at 2 months using Fast MRI, and 3 at 6 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fast MRI | End Diastolic Volume (EDV) at Baseline, 2 Month, and 6 Months | 2 months FAST MRI | 126.07 mL | Standard Deviation 32.36 |
| Fast MRI | End Diastolic Volume (EDV) at Baseline, 2 Month, and 6 Months | 6 months | 130.20 mL | Standard Deviation 44.52 |
Comparison: Correlation between baseline and 2 months.p-value: 0.9395Pearson Correlation Coefficient
Comparison: Correlation between baseline and 6 months.p-value: 0.1486Pearson Correlation Coefficient
Primary
End Systolic Volume (ESV) at Baseline, 2 Month, and 6 Months
To compare baseline, 2-month (using Fast MRI), and 6 month measures in end Systolic Volume (ESV)
Time frame: Baseline, 2 months, and 6 months
Population: Only 5 received MRI at baseline, 4 at 2 months using Fast MRI, and 3 at 6 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fast MRI | End Systolic Volume (ESV) at Baseline, 2 Month, and 6 Months | 2 months FAST MRI | 54.72 mL | Standard Deviation 14.52 |
| Fast MRI | End Systolic Volume (ESV) at Baseline, 2 Month, and 6 Months | 6 months | 54.73 mL | Standard Deviation 23.11 |
Comparison: Correlation between baseline and 2 months.p-value: 0.9341Pearson Correlation Coefficient
Comparison: Correlation between baseline and 6 months.p-value: 0.0497Pearson Correlation Coefficient
Primary
Left Ventricular Ejection Fraction (LVEF) at Baseline, 2 Month Using Fast MRI, and 6 Months
To compare baseline, 2-month (using Fast MRI), and 6 month measures in left ventricular (LV) ejection fraction
Time frame: Baseline, 2 months, and 6 months
Population: Only 5 received MRI at baseline, 4 at 2 months using Fast MRI, and 3 at 6 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fast MRI | Left Ventricular Ejection Fraction (LVEF) at Baseline, 2 Month Using Fast MRI, and 6 Months | 2 months FAST MRI | 56.67 percentage of fluid ejected | Standard Deviation 4.71 |
| Fast MRI | Left Ventricular Ejection Fraction (LVEF) at Baseline, 2 Month Using Fast MRI, and 6 Months | 6 months | 58.69 percentage of fluid ejected | Standard Deviation 3.28 |
Comparison: Correlation between baseline and 2 months.p-value: 0.6102Pearson Correlation Coefficient
Comparison: Correlation between baseline and 6 months.p-value: 0.8343Peason Correlation Coefficient
Primary
Pulse Wave Velocity (PWV) at Baseline and 6 Months
To compare baseline and 6 month measures in pulse wave velocity (PWV)
Time frame: Baseline and 6 months
Population: Only 5 received MRI at baseline and 3 at 6 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fast MRI | Pulse Wave Velocity (PWV) at Baseline and 6 Months | Baseline | 4.74 Meters/sec | Standard Deviation 1.75 |
| Fast MRI | Pulse Wave Velocity (PWV) at Baseline and 6 Months | 6 months | 4.07 Meters/sec | Standard Deviation 1.7 |
p-value: 0.1129Pearson Correlation Coefficient
Secondary
End Diastolic Volume (EDV): Compare Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline
To compare magnetic resonance imaging (MRI) metric of End Diastolic Volume (EDV) with echocardiogram (ECHO) at baseline
Time frame: Baseline
Population: All 6 participants that received both an ECHO. Only 5 had an MRI at baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fast MRI | End Diastolic Volume (EDV): Compare Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline | EDV Echo | 100.08 mL | Standard Deviation 24.2 |
| Fast MRI | End Diastolic Volume (EDV): Compare Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline | EDV MRI | 134.90 mL | Standard Deviation 41.7 |
Secondary
End Systolic Volume (ESV): Compare Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline
To compare magnetic resonance imaging (MRI) metric of End Systolic Volume (ESV) with echocardiogram (ECHO) at baseline
Time frame: Baseline
Population: All 6 participants that received both an ECHO. Only 5 had an MRI at baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fast MRI | End Systolic Volume (ESV): Compare Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline | ESV Echo | 44.90 mL | Standard Deviation 9.16 |
| Fast MRI | End Systolic Volume (ESV): Compare Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline | ESV MRI | 52.23 mL | Standard Deviation 18.91 |
Secondary
Left Ventricular Ejection Fraction (LVEF): Comparison of Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline
To compare Magnetic Resonance Imaging (MRI) metric of Left Ventricular Ejection Fraction (LVEF) with Echocardiogram (ECHO) at baseline
Time frame: Baseline
Population: All 6 participants that received both an ECHO. Only 5 had an MRI at baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fast MRI | Left Ventricular Ejection Fraction (LVEF): Comparison of Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline | LVEF Echo | 54.17 percentage of fluid expelled | Standard Deviation 7.03 |
| Fast MRI | Left Ventricular Ejection Fraction (LVEF): Comparison of Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline | LVEF MRI | 61.51 percentage of fluid expelled | Standard Deviation 5.45 |
Other Pre-specified
Exploratory Algorithmic Modeling
To use exploratory algorithmic modeling to obtain optimal strategies for determining the combination of metrics (10-min MR, ECHO, serum biomarkers) at 2-months that predict the 6-month post Chemotherapy deteriorations in cardiovascular function.
Time frame: Baseline to 6 months