Breast Cancer, Cardiotoxicity, Heart Disease, Myocardial Dysfunction
Conditions
Keywords
Statin therapy, trastuzumab
Brief summary
The purpose of this study is to to examine the effects of atorvastatin, a type of statin, on changes to the heart among women undergoing breast cancer treatment. Atorvastatin may reduce or eliminate the harmful effects of chemotherapy treatment to the heart tissue of breast cancer patients.
Detailed description
This is a placebo-controlled study. It will compare the effects of atorvastatin against the effects of a placebo (an inactive substance, such as, a sugar pill) on changes to the heart before and during breast cancer treatment. Participants will be in the study for approximately a year and a half, and the study will enroll up to 60 patients. During that time, there will be six visits that may coincide with standard of care visits. Participants will also receive telephone calls from study staff during the study intervention and a follow-up phase to check-in with them.
Interventions
DRUGAtorvastatin
Atorvastatin calcium, a synthetic lipid-lowering agent, is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in cholesterol biosynthesis.
DRUGPlacebo
A substance that has no therapeutic effect, and will be used as a control in testing the study agent.
Sponsors
California Breast Cancer Research Program
Cedars-Sinai Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female patients with newly diagnosed stage 1-3 breast cancer * Histologically confirmed HER2, ER, and PR status * Recommended to undergo trastuzumab treatment, with or without anthracycline. Patients will be eligible for up to 3 weeks after starting treatment. * Age minimum 18 years * Able and willing to read, understand, and sign an informed consent form (ICF) and medical release form * Willing and able to comply with trial protocol and follow-up * ECOG performance status 0-1 (Karnofsky ≥ 70%)
Exclusion criteria
* Prior use of statin medication within the past year * Not using statin medication but is eligible for statin therapy based on the 2013 ACC/AHA guidelines (LDL cholesterol \>190, or LDL \<190 and ASCVD risk \>7.5%; http://tools.acc.org/ASCVD-Risk-Estimator/) and is \> 50 years old; or is eligible for statin therapy based on the 2013 ACC/AHA guidelines and is 40-50 years old and wishes to be placed on statin therapy * History of adverse effects, intolerance, or allergic reactions attributed to statin medication * Current use of gemfibrozil, cyclosporine, clarithromycin, itraconazole, erythromycin, the hepatitis C protease inhibitor telaprevir, HIV protease inhibitors, colchicine, or red yeast rice * Current use of any other investigational agent * Pregnant or intention to get pregnant during the next 18 months. Pregnant women are excluded from this study because atorvastatin is a lipid-lowering agent with the potential for teratogenic or abortifacient effects, and MRI is contraindicated in pregnant women. * History of diabetes, severe lung disease, renal disease (creatinine \> 1.8 mg/dL or CrCl ≤ 50 mL/min), or hepatic disease (AST and ALT \> 3 times upper normal limits) * Abnormal baseline echocardiogram or cardiac MRI (detection of congenital heart disease; ischemic heart disease; moderate or severe valvular heart disease; cardiomyopathy; EF \< 55%) * Previously known or diagnosed heart disease (e.g. congenital; valvular; coronary artery disease; history of myocardial infarction or acute coronary syndrome; cardiomyopathy, including infiltrative, hypertensive, hypertrophic, dilated, constrictive pericarditis, or other cardiomyopathy) * Left ventricular dysfunction (EF \< 55%) * Prior non-cardiac illness with an estimated life expectancy \< 4 years * Known active infection with HIV * Allergy or contraindication to MRI testing, including claustrophobia, metallic parts in body the prohibiting MRI, prior gadolinium contrast reaction, or uncontrolled moderate hypertension (sitting blood pressure \>160/95 mm Hg with measurements recorded on at least 2 occasions). * Has metallic breast expanders in place at the time of screening * Concurrent illness which in the opinion of the investigators would compromise either the patient or the integrity of the data
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Global Circumferential Strain (GCS) Measured by Cardiac MRI (CMRI) | baseline to 12 months post initiation of statin intervention |
Secondary
| Measure | Time frame |
|---|---|
| Change in Peak Left Ventricular Twist as Measured by CMRI | Baseline to 12 months of follow-up |
| Change in Peak Left Ventricular Torsion as Measured by CMRI | Baseline to 12 months of follow-up |
| Change in Left Ventricular Untwisting Rate as Measured by CMRI | Baseline to 12 months of follow-up |
| Change in Left Ventricular Ejection Fraction as Measured by CMRI | Baseline to 12 months of follow-up |
| Change in Left Ventricular End Diastolic Volume as Measured by CMRI | Baseline to 12 months of follow-up |
| Change in Left Ventricular End Systolic Volume as Measured by CMRI | Baseline to 12 months of follow-up |
| Change in Global Longitudinal Strain as Measured by CMRI | Baseline to 12 months of follow-up |
| Change in Left Ventricular Mass as Measured by CMRI | Baseline to 12 months of follow-up |
| Change in Left Ventricular Concentricity as Measured by CMRI | Baseline to 12 months of follow-up |
| Change in Native T1 as Measured by CMRI | Baseline to 12 months of follow-up |
| Change in Post Contrast T1 as Measured by CMRI | Baseline to 12 months of follow-up |
| Change in Extracellular Volume as Measured by CMRI | Baseline to 12 months of follow-up |
| Change in Native T2 as Measured by CMRI | Baseline to 12 months of follow-up |
| Change in Cardiac Output as Measured by CMRI | Baseline to 12 months of follow-up |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Agent One atorvastatin 20 mg oral capsule per day
Atorvastatin: Atorvastatin calcium, a synthetic lipid-lowering agent, is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in cholesterol biosynthesis. | 1 |
| Control One matching placebo daily
Placebo: A substance that has no therapeutic effect, and will be used as a control in testing the study agent. | 1 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Study Agent | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 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 / 1 | 0 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 1 / 1 |
Outcome results
Primary
Change in Global Circumferential Strain (GCS) Measured by Cardiac MRI (CMRI)
Time frame: baseline to 12 months post initiation of statin intervention
Population: As accrual fell well below target, change in global circumferential strain (GCS) measured by Cardiac MRI (CMRI) was not calculated.
Secondary
Change in Cardiac Output as Measured by CMRI
Time frame: Baseline to 12 months of follow-up
Population: As accrual fell well below target, change in cardiac output as measured by CMRI was not calculated.
Secondary
Change in Extracellular Volume as Measured by CMRI
Time frame: Baseline to 12 months of follow-up
Population: As accrual fell well below target, change in extracellular volume as measured by CMRI was not calculated.
Secondary
Change in Global Longitudinal Strain as Measured by CMRI
Time frame: Baseline to 12 months of follow-up
Population: As accrual fell well below target, change in global longitudinal strain as measured by CMRI was not calculated.
Secondary
Change in Left Ventricular Concentricity as Measured by CMRI
Time frame: Baseline to 12 months of follow-up
Population: As accrual fell well below target, change in left ventricular concentricity as measured by CMRI was not calculated.
Secondary
Change in Left Ventricular Ejection Fraction as Measured by CMRI
Time frame: Baseline to 12 months of follow-up
Population: As accrual fell well below target, change in left ventricular ejection fraction as measured by CMRI was not calculated.
Secondary
Change in Left Ventricular End Diastolic Volume as Measured by CMRI
Time frame: Baseline to 12 months of follow-up
Population: As accrual fell well below target, change in left ventricular end diastolic volume as measured by CMRI was not calculated.
Secondary
Change in Left Ventricular End Systolic Volume as Measured by CMRI
Time frame: Baseline to 12 months of follow-up
Population: As accrual fell well below target, change in left ventricular end systolic volume as measured by CMRI was not calculated.
Secondary
Change in Left Ventricular Mass as Measured by CMRI
Time frame: Baseline to 12 months of follow-up
Population: As accrual fell well below target, change in left ventricular mass as measured by CMRI was not calculated.
Secondary
Change in Left Ventricular Untwisting Rate as Measured by CMRI
Time frame: Baseline to 12 months of follow-up
Population: As accrual fell well below target, change in left ventricular untwisting rate as measured by CMRI was not calculated.
Secondary
Change in Native T1 as Measured by CMRI
Time frame: Baseline to 12 months of follow-up
Population: As accrual fell well below target, change in native T1 as measured by CMRI was not calculated.
Secondary
Change in Native T2 as Measured by CMRI
Time frame: Baseline to 12 months of follow-up
Population: As accrual fell well below target, change in native T2 as measured by CMRI was not calculated.
Secondary
Change in Peak Left Ventricular Torsion as Measured by CMRI
Time frame: Baseline to 12 months of follow-up
Population: As accrual fell well below target, change in peak left ventricular torsion as measured by CMRI was not calculated.
Secondary
Change in Peak Left Ventricular Twist as Measured by CMRI
Time frame: Baseline to 12 months of follow-up
Population: As accrual fell well below target, change in peak left ventricular twist as measured by CMRI was not calculated.
Secondary
Change in Post Contrast T1 as Measured by CMRI
Time frame: Baseline to 12 months of follow-up
Population: As accrual fell well below target, change in post contrast T1 as measured by CMRI was not calculated.