Heart and Blood Diseases

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Heart Diseases

Breast Neoplasms

Cardiotoxicity

Breast Diseases

Skin Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Antineoplastic Agents

All Drugs and Chemicals

Lipid Regulating Agents

Bone Density Conservation Agents

Trastuzumab

Calcium

Atorvastatin

Calcium, Dietary

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Hypolipidemic Agents

Anticholesteremic Agents

Antimetabolites

Enzyme Inhibitors

One atorvastatin 20 mg oral capsule per day

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.

A substance that has no therapeutic effect, and will be used as a control in testing the study agent.

Placebo

Marc Goodman, PhD

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.

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.

STOP Heart Disease in Breast Cancer Survivors Trial

Statin Therapy Operates to Prevent (STOP) Heart Disease in Breast Cancer Survivors Trial

California Breast Cancer Research Program

Cedars-Sinai Medical Center

Professor and Director, Cancer Prevention & Control - Department, Cancer Institute

Regular investigator assessment, regular laboratory testing, self-reporting.

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.

Study Agent

One matching placebo daily

Placebo: A substance that has no therapeutic effect, and will be used as a control in testing the study agent.

Control

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Accrual fell well below target. Two subjects were randomized to the study and one subject completed the study. Outcome measures were not analyzed due to insufficient accrual.

As accrual fell well below target, change in global circumferential strain (GCS) measured by Cardiac MRI (CMRI) was not calculated.

Change in Global Circumferential Strain (GCS) Measured by Cardiac MRI (CMRI)

As accrual fell well below target, change in global longitudinal strain as measured by CMRI was not calculated.

Change in Global Longitudinal Strain as Measured by CMRI

As accrual fell well below target, change in peak left ventricular twist as measured by CMRI was not calculated.

Change in Peak Left Ventricular Twist as Measured by CMRI

As accrual fell well below target, change in peak left ventricular torsion as measured by CMRI was not calculated.

Change in Peak Left Ventricular Torsion as Measured by CMRI

As accrual fell well below target, change in left ventricular untwisting rate as measured by CMRI was not calculated.

Change in Left Ventricular Untwisting Rate as Measured by CMRI

As accrual fell well below target, change in left ventricular ejection fraction as measured by CMRI was not calculated.

Change in Left Ventricular Ejection Fraction as Measured by CMRI

As accrual fell well below target, change in left ventricular end diastolic volume as measured by CMRI was not calculated.

Change in Left Ventricular End Diastolic Volume as Measured by CMRI

As accrual fell well below target, change in left ventricular end systolic volume as measured by CMRI was not calculated.

Change in Left Ventricular End Systolic Volume as Measured by CMRI

As accrual fell well below target, change in cardiac output as measured by CMRI was not calculated.

Change in Cardiac Output as Measured by CMRI

As accrual fell well below target, change in left ventricular mass as measured by CMRI was not calculated.

Change in Left Ventricular Mass as Measured by CMRI

As accrual fell well below target, change in left ventricular concentricity as measured by CMRI was not calculated.

Change in Left Ventricular Concentricity as Measured by CMRI

As accrual fell well below target, change in native T1 as measured by CMRI was not calculated.

Change in Native T1 as Measured by CMRI

As accrual fell well below target, change in post contrast T1 as measured by CMRI was not calculated.

Change in Post Contrast T1 as Measured by CMRI

As accrual fell well below target, change in extracellular volume as measured by CMRI was not calculated.

Change in Extracellular Volume as Measured by CMRI

As accrual fell well below target, change in native T2 as measured by CMRI was not calculated.

Change in Native T2 as Measured by CMRI

Overall Study

Nervous System Diseases

Stroke

Atherosclerosis

Ischemia

Ischemic Attack, Transient

Arteriosclerosis

Arterial Occlusive Diseases

Vascular Diseases

Anti-Infective Agents

Central Nervous System Depressants

Ethanol

Rosuvastatin Calcium

Lifestyle modification is tailored to each participant and includes a recommended exercise regimen, a healthy diet and decreasing alcohol intake.

Participants will receive statin medication along with instruction about regular exercise.

Statin therapy includes rosuvastatin 20 mg administered orally, once a day, for the duration of the trial, which is 3 years. Participants may also receive a different type of statin as prescribed by their cardiologist based on clinical judgement.

Statin therapy

Lifestyle modification includes a recommended exercise regimen, a healthy diet and decreasing alcohol intake for 3 years.

Lifestyle modification

John Oshinski, PhD

The goal of this study is to assess a slimy substance that settles/deposits along blood vessel wall. This slimy substance is called plaque. Plaque could be made up of fat, calcium or both. Plaque deposition narrows the vessels. This leads to decreased blood flow to various parts of body. Blood vessels include vessels that supply to heart (coronary), vessels to brain (carotid), vessels to kidneys (renal) and vessels to legs (femoral). Decreased blood flow causes symptoms such as brain stroke, heart attack, leg pain. Similarly individuals at risk of cardiovascular disease can have certain markers elevated in their blood that can be measured by simple blood tests.

High or increased plaque deposition is seen in neck vessels of cancer patients who received radiation to chest or head and neck as part of their cancer treatment. Cancer survivors are at increased risk of plaque development and are therefore called high-risk population. Exercise +/- fat lowering medicine can potentially decrease plaque deposition and statins are one of the several fat lowering medications.

Cardiovascular disease (CVD) and cancer are the leading causes of suffering and death amongst the American population. While an ever-increasing number of cancer survivors have a favorable outcome due to advances in cancer treatment; cancer survivors remain at high risk of developing CVD at an early age. There is scant information available on the pathogenic process that contributes to cardiovascular threat amongst cancer survivors and little is known about the interventions, which may interrupt or decrease the risk of CVD in this population. Importantly, early-subclinical markers may substantially precede clinical markers.

The objective of this project is to accurately determine the constituents and characteristics of atherosclerotic plaques in carotid arteries by magnetic resonance imaging (MRI) techniques in cancer survivors; at different data intervals: before and after administration of treatment (medical and life style modification) and then correlate contrast agent dynamics with serum markers of inflammation and other tests of cardiac or vascular dysfunction, where available.

The proposed study involves 100 asymptomatic patients who received prior chest or head and neck radiation therapy (HNXRT) as part of cancer treatment. MRI data (direct assessment of atherosclerosis) would be correlated with indirect measures of atherosclerosis (blood surrogate markers \& metabolomics).

The investigators intend to conduct an initial baseline MRI, blood tests (to correlate with surrogate markers of inflammation) and other tests whenever available of cardiac or vascular dysfunction. This cohort will be followed up with medication and/or life style modification regimen for a period of initially18 months and subsequently at 36 months. A repeat of all baseline studies (MRI and blood tests) would be performed as part of the 18 and 36-month follow-up. The plaque characteristics found at MRI will be correlated with results of blood tests (baseline, 18 and 36 months) and changes in one or both will be the expected end point of the study.

The protocol originally specified randomizing participants to a study arm, but the protocol was amended to clarify that a participant's cardiologist could change the treatment regimens that participants were assigned to so that no participant was restricted from statin therapy.

Accelerated Atherosclerosis in High Risk Population Groups: An Assessment by Magnetic Resonance Imaging

Plaque volume of carotid arteries were measured by MRI as a surrogate for progression of cardiovascular disease. Plaque volume varies with observed ranges from other studies ranging from 23.9 to 604.1mm\^3. Plaque volume tends to increase with age. Increased plaque volume has an increased risk of vascular events.

Emory University

Associate Professor

All adverse events were graded as to their attribution (unrelated to protocol, or possibly, probably, or definitely related to protocol). All serious or unexpected adverse experiences and all deaths were recorded and reported according to the National Cancer Institute Common Toxicity Criteria. Serious adverse events were not expected to occur in this study due to the low risk involved with the study procedures performed.

Participants receiving information about lifestyle modifications including a recommended exercise regimen, a healthy diet and decreasing alcohol intake.

Lifestyle Modification

Participants receiving statin therapy. A participant's cardiologist could change the treatment regimen that a participant was assigned to so that no participant was restricted from statin therapy. The results reflect the treatment each participant actually received rather than the treatment each participant was randomized to.

Statin Therapy

Age, Continuous

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United States

Region of Enrollment

All participants who began the intervention are included in the baseline analysis population description.

John Oshinski PhD

Baseline

Month 18

Month 36

This analysis includes all participants who completed the MRI at each time point. Most participants did not return for the follow up MRI measurements.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
STOP Heart Disease in Breast Cancer Survivors Trial	NCT02674204	Breast Cancer Heart Disease Cardiotoxicity Myocardial Dysf...	Atorvastatin Placebo	18 Years -	Cedars-Sinai Medical Center
Accelerated Atherosclerosis in High Risk Population Groups: An Assessment by Magnetic Resonance Imaging	NCT02114697	Atherosclerosis	Statin therapy Lifestyle modif...	22 Years -	Emory University
STOP Heart Disease in Breast Cancer Survivors Trial	NCT02674204	Breast Cancer Heart Disease Cardiotoxicity Myocardial Dysf...	Atorvastatin Placebo	18 Years -	Cedars-Sinai Medical Center
STOP Heart Disease in Breast Cancer Survivors Trial	NCT02674204	Breast Cancer Heart Disease Cardiotoxicity Myocardial Dysf...	Atorvastatin Placebo	18 Years -	Cedars-Sinai Medical Center
STOP Heart Disease in Breast Cancer Survivors Trial	NCT02674204	Breast Cancer Heart Disease Cardiotoxicity Myocardial Dysf...	Atorvastatin Placebo	18 Years -	Cedars-Sinai Medical Center

Spots Global Cancer Trial Database for statin therapy