Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)

NCT ID: NCT01988571

Last Updated: 2022-01-04

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

279 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-02-01

Study Completion Date

2020-09-24

Brief Summary

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The purpose of this research study is to see if Atorvastatin (Lipitor) 40 mg by mouth daily decreases the chance of developing heart problems in individuals receiving adjuvant anthracycline-based chemotherapy for breast cancer of lymphoma.

Detailed Description

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PRIMARY OBJECTIVES:

Specific Aim 1:

To determine if Atorvastatin(Lipitor) administration preserves left ventricular ejection fraction (LVEF) 24 months after initiation of Anthracycline-based adjuvant therapy for adjuvant treatment of breast cancer or lymphoma.

Specific Aim 2:

To determine if baseline to 6-month differences in LVEF predict baseline to 24-month differences in LVEF after Anthracycline-based adjuvant therapy and concomitant atorvastatin therapy.

To achieve these aims, we will perform a double-blind, placebo-controlled, randomized clinical trial of 0 or 40 mg of atorvastatin/day in 278 individuals scheduled to receive Anthracycline-based chemotherapy for treatment of Stage I-III breast cancer or lymphoma Stage I-IV with a projected \> 2 year life expectancy. We will use innovative noninvasive magnetic resonance imaging (MRI) procedures to accurately measure LVEF. In addition, we will measure left ventricle (LV) volumes, myocardial strain, fibrosis, aortic pulse wave velocity (PWV) and wall thickness, all factors that can influence LVEF by altering LV pre-load, after-load, and contractility.19,20 Advanced serum biomarkers will be measured that assess for the presence of oxidative/nitrosative stress, systemic inflammation and circulating neurohormones that also may influence LVEF.

This study will test a new clinical paradigm to manage breast cancer: primary prevention of Anthracycline-based adjuvant therapy-related LV dysfunction using pre-treatment with low-cost statins. In addition, this trial will be the first systematic collection of data regarding the mechanism(s) and time course by which LV dysfunction and subsequent chronic heart failure (CHF) evolve in individuals given Anthracycline-based chemotherapy for breast cancer or lymphoma. These data will be useful to physicians trying to determine the optimal cardiac protection strategies when administering adjuvant chemotherapeutic regimens to their breast cancer or lymphoma patients. The objective of this research is to use inexpensive medications to preserve cardiovascular (CV) health and thereby improve overall survival in the growing number of breast cancer and lymphoma patients.

SECONDARY OBJECTIVES

Specific Aim 1:

To document the effect of Atorvastatin (Lipitor) on cognitive function using a battery of neurocognitive tests (HVLT, Rey-osterrieth Figure, controlled oral word association test (COWA), Trail-making Parts A and B, Digit Span and Grooved Pegboard) in breast cancer and lymphoma patients receiving an anthracycline.

Specific Aim 2:

To document the effect of Atorvastatin(Lipitor) on self-reported quality of life using validated questionnaires (PROMIS including: General form, Cog Concerns, Cog Abilities, Fatigue, Pain intensity and interference, Sleep Disturbance, Physical Functioning and Social Functioning) in breast cancer and lymphoma patients receiving an anthracycline.

Conditions

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Breast Cancer Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Arm 1 - Atorvastatin

One 40 mg Atorvastatin tablet each morning by mouth for 24 months

Group Type ACTIVE_COMPARATOR

Atorvastatin

Intervention Type DRUG

40 mg tablet taken by mouth each morning for 24 months.

Arm 2 - Placebo

One placebo tablet each morning by mouth for 24 months.

Group Type PLACEBO_COMPARATOR

Atorvastatin

Intervention Type DRUG

40 mg tablet taken by mouth each morning for 24 months.

Placebo

Intervention Type DRUG

One placebo tablet taken each morning orally for 24 months.

Interventions

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Atorvastatin

40 mg tablet taken by mouth each morning for 24 months.

Intervention Type DRUG

Placebo

One placebo tablet taken each morning orally for 24 months.

Intervention Type DRUG

Other Intervention Names

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Lipitor sugar pill

Eligibility Criteria

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Inclusion Criteria

* Stage I-III breast cancer (including inflammatory and newly diagnosed recurrent breast cancer) or lymphoma Stage I-IV. (Patients should have a \> 2 year life expectancy)
* Scheduled to receive adjuvant chemotherapy with an Anthracycline (doxorubicin and epirubicin)
* 21 years of age or older
* LVEF \> 50% (Most recent within the last 5 years)
* Prior administration of anthracyclines is acceptable if therapy was completed \> 6 months prior to study enrollment
* Patients that are receiving or have received chemotherapy regimens are allowed
* Able to hold breath for 10 seconds
* Prior cancers allowed if no evidence of disease in last 5 years
* Eastern Cooperative Oncology Group (ECOG) 0 or 1

Exclusion Criteria

* Prior use of lipid-lowering therapy within the last 6 months
* Current postmenopausal hormone-replacement therapy
* Uncontrolled hypertension (systolic blood pressure \>190 mm Hg or diastolic blood pressure \>100 mm Hg)
* Scheduled to receive neoadjuvant chemotherapy with an anthracycline
* No active liver disease allowed
* Uncontrolled hypothyroidism
* Recent history (within past 3 years) of alcohol or drug abuse, inflammatory conditions such as lupus or inflammatory bowel disease, use of immunosuppressant agents, or another medical condition that might compromise safety or the successful completion of the study.
* Patients with ferromagnetic cerebral aneurysm clips or other intraorbital/intracranial metal;pacemakers, defibrillators, functioning neurostimulator devices or other implanted electronic devices.
* Unstable angina; significant ventricular arrhythmias (\>20 premature ventricular complexes (PVCs)/min due to gating difficulty) atrial fibrillation with uncontrolled ventricular response; coronary artery disease; acute myocardial infarction within 28 days
* Current use of Cytochrome P450 (CYP3A4) inhibitors. These include Clarithromycin, HIV protease inhibitors, Itraconazole, grapefruit juice, Cyclosporine, Rifampin or Digoxin
* Current or history of hepatic dysfunction
* Unable to provide informed consent
* Claustrophobia
* Planning to move within 24 months of trial enrollment
* Pregnant or breast-feeding
Minimum Eligible Age

21 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gregory Hundley, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

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Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Site Status

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Cancer Center of Kansas-Wichita Medical Arts Tower

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas - Wichita

Wichita, Kansas, United States

Site Status

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, United States

Site Status

William Beaumont Hospital-Royal Oak

Royal Oak, Michigan, United States

Site Status

William Beaumont Hospital - Troy

Troy, Michigan, United States

Site Status

Saint John's Hospital - Healtheast

Maplewood, Minnesota, United States

Site Status

Abbott-Northwestern Hospital

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota, United States

Site Status

Regions Hospital

Saint Paul, Minnesota, United States

Site Status

United Hospital

Saint Paul, Minnesota, United States

Site Status

Mission Hospital

Asheville, North Carolina, United States

Site Status

Hope Women's Cancer Centers-Asheville

Asheville, North Carolina, United States

Site Status

Cone Health Cancer Center at Alamance Regional

Burlington, North Carolina, United States

Site Status

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Site Status

Oncology Specialists of Charlotte

Charlotte, North Carolina, United States

Site Status

Cone Health Cancer Center

Greensboro, North Carolina, United States

Site Status

Novant Health Cancer Institute - Huntersville

Huntersville, North Carolina, United States

Site Status

Southern Oncology Specialists-Huntersville

Huntersville, North Carolina, United States

Site Status

Novant Health Cancer Institute - Kernersville

Kernersville, North Carolina, United States

Site Status

Novant Health Cancer Specialists-Matthews

Matthews, North Carolina, United States

Site Status

Novant Health Forsyth Medical Center

Winston-Salem, North Carolina, United States

Site Status

Novant Health Oncology Specialists

Winston-Salem, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Columbus Oncology and Hematology Associates Inc

Columbus, Ohio, United States

Site Status

Doctors Hospital

Columbus, Ohio, United States

Site Status

Delaware Health Center-Grady Cancer Center

Delaware, Ohio, United States

Site Status

Genesis Healthcare System Cancer Care Center

Zanesville, Ohio, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Easley

Easley, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Butternut

Greenville, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Faris

Greenville, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Eastside

Greenville, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Seneca

Seneca, South Carolina, United States

Site Status

Centra Lynchburg Hematology-Oncology Clinic Inc

Lynchburg, Virginia, United States

Site Status

Virginia Cancer Institute

Richmond, Virginia, United States

Site Status

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Site Status

Shenandoah Oncology PC

Winchester, Virginia, United States

Site Status

Aurora Cancer Care-Southern Lakes VLCC

Burlington, Wisconsin, United States

Site Status

Aurora Cancer Care-Grafton

Grafton, Wisconsin, United States

Site Status

Vince Lombardi Cancer Clinic - Oshkosh

Oshkosh, Wisconsin, United States

Site Status

Aurora Medical Center in Summit

Summit, Wisconsin, United States

Site Status

Countries

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United States

References

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Grizzard PJ, O'Connell NS, Rapp SR, Olson KC, Bellissimo MP, Hughes AN, Ladd AC, Weaver KE, Wagner LI, Ruddy KJ, Ky B, D'Agostino RB, Hundley WG. Preserved Cognitive Function After Statin Administration During Cancer Treatment With Doxorubicin: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2025 Oct 1;8(10):e2538325. doi: 10.1001/jamanetworkopen.2025.38325.

Reference Type DERIVED
PMID: 41118164 (View on PubMed)

Sutton AL, O'Connell NS, Lucas AR, Olson KC, Reding KW, Sheppard VB, Ky B, Ruddy KJ, Weaver KE, Hundley WG. Socioeconomic status and left ventricular ejection fraction decline in breast cancer survivors following receipt of doxorubicin (PREVENT WF-98213). Cardiooncology. 2025 Feb 5;11(1):11. doi: 10.1186/s40959-025-00311-y.

Reference Type DERIVED
PMID: 39910652 (View on PubMed)

Hundley WG, D'Agostino R Jr, Crotts T, Craver K, Hackney MH, Jordan JH, Ky B, Wagner LI, Herrington DM, Yeboah J, Reding KW, Ladd AC, Rapp SR, Russo S, O'Connell N, Weaver KE, Dressler EV, Ge Y, Melin SA, Gudena V, Lesser GJ. Statins and Left Ventricular Ejection Fraction Following Doxorubicin Treatment. NEJM Evid. 2022 Sep;1(9):10.1056/evidoa2200097. doi: 10.1056/evidoa2200097. Epub 2022 Aug 18.

Reference Type DERIVED
PMID: 36908314 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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U10CA081851

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R01HL118740-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

REBACCCWFU 98213

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2013-01760

Identifier Type: REGISTRY

Identifier Source: secondary_id

IRB00038639

Identifier Type: -

Identifier Source: org_study_id

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