STOP Heart Disease in Breast Cancer Survivors Trial (STOP)

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

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer; Heart Disease; Cardiotoxicity; Myocardial Dysfunction
• Intervention / Treatment: Drug: Atorvastatin; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Agent; One atorvastatin 20 mg oral capsule per day	Drug: 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.; Other Names: Lipitor; Atorvastatin calcium
Placebo Comparator: Control; One matching placebo daily	Drug: Placebo; A substance that has no therapeutic effect, and will be used as a control in testing the study agent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Global Circumferential Strain (GCS) Measured by Cardiac MRI (CMRI)	baseline to 12 months post initiation of statin intervention

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Global Longitudinal Strain as Measured by CMRI	Baseline to 12 months of follow-up
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 Cardiac Output 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

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Collaborators: California Breast Cancer Research Program
• Investigators: Principal Investigator: Marc Goodman, PhD, Cedars-Sinal Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2016
• Primary Completion (Actual): May 25, 2018
• Study Completion (Actual): May 25, 2018

Study Registration Dates

• First Submitted: January 21, 2016
• First Submitted That Met QC Criteria: February 2, 2016
• First Posted (Estimate): February 4, 2016

Study Record Updates

• Last Update Posted (Actual): May 15, 2019
• Last Update Submitted That Met QC Criteria: May 1, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: trastuzumab; Statin therapy
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Cardiovascular Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Wounds and Injuries; Breast Diseases; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Heart Diseases; Breast Neoplasms; Cardiotoxicity; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: IIT2015-12-Goodman-STOP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No