STOP Heart Disease in Breast Cancer Survivors Trial

NCT02674204 | Terminated Phase 2 Results DMC

• 1 other identifier: IIT2015-12-Goodman-STOP
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; Heart Disease; Cardiotoxicity; Myocardial Dysfunction

Keywords

Statin therapy; trastuzumab

Outcome Measures

Primary Outcomes (1)

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

  baseline to 12 months post initiation of statin intervention

Secondary Outcomes (14)

• 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

Study Arms (2)

Study Agent

EXPERIMENTAL

One atorvastatin 20 mg oral capsule per day

Drug: Atorvastatin

Control

PLACEBO COMPARATOR

One matching placebo daily

Drug: Placebo

Interventions

Atorvastatin DRUG

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.

Also known as: Lipitor, Atorvastatin calcium

Study Agent

Placebo DRUG

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

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%)

You may not qualify if:

• 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

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• California Breast Cancer Research Program: collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Heart Diseases; Cardiotoxicity

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Limitations and Caveats

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.

Results Point of Contact

• Title: Marc Goodman, PhD
• Organization: Cedars-Sinai Medical Center

Marc.Goodman@cshs.org

310-423-6188

Study Officials

• Marc Goodman, PhD

  Cedars-Sinal Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Director, Cancer Prevention & Control - Department, Cancer Institute

Study Record Dates

• First Submitted: January 21, 2016
• First Posted: February 4, 2016
• Study Start: May 5, 2016
• Primary Completion: May 25, 2018
• Study Completion: May 25, 2018
• Last Updated: May 15, 2019
• Results First Posted: April 30, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)