Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)

Breast Cancer Clinical Trial

Official title:

Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01988571
• Other study ID #: IRB00038639
• Secondary ID: U10CA0818511R01H
• Status: Completed
• Phase: Phase 2
• Start date: February 1, 2014
• Est. completion date: September 24, 2020

Study information

• Verified date: December 2021
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 279
• Est. completion date: September 24, 2020
• Est. primary completion date: September 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Lymphoma

Intervention

Drug:
• Atorvastatin
40 mg tablet taken by mouth each morning for 24 months.
• Placebo
One placebo tablet taken each morning orally for 24 months.

Locations

Country	Name	City	State
United States	Hope Women's Cancer Centers-Asheville	Asheville	North Carolina
United States	Mission Hospital	Asheville	North Carolina
United States	Tufts Medical Center	Boston	Massachusetts
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	Oncology Specialists of Charlotte	Charlotte	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Novant Health Cancer Institute - Huntersville	Huntersville	North Carolina
United States	Southern Oncology Specialists-Huntersville	Huntersville	North Carolina
United States	Novant Health Cancer Institute - Kernersville	Kernersville	North Carolina
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Centra Lynchburg Hematology-Oncology Clinic Inc	Lynchburg	Virginia
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Novant Health Cancer Specialists-Matthews	Matthews	North Carolina
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Shenandoah Oncology PC	Winchester	Virginia
United States	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina
United States	Novant Health Oncology Specialists	Winston-Salem	North Carolina
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Left Ventricular Ejection Fraction (LVEF)	24 month estimated values of clinical measurements obtained from Cardiac MRI left ventricular ejection fraction by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.	24 months
Secondary	End Diastolic Volume	24 month estimated values of clinical measurements obtained from Cardiac MRI End Diastolic Volume by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.	24 months
Secondary	End Systolic Volume	24 month estimated values of clinical measurements obtained from Cardiac MRI End Systolic Volume by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.	24 months
Secondary	Stroke Volume	24 month estimated values of clinical measurements obtained from Cardiac MRI Stroke Volume by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.	24 months
Secondary	Left Ventricular (LV) Mass	24 month estimated values of clinical measurements obtained from Cardiac MRI left ventricular mass by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.	24 months
Secondary	Pulse Wave Velocity	24 month estimated values of clinical measurements obtained from Cardiac MRI pulse wave velocity by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.	24 months
Secondary	Hopkins Verbal Learning Test (HVLT) Total Recall	24 month estimated values Hopkins Verbal Learning test (HVLT) total recall by group. Linear model adjusts for baseline value and group assignment. No missing imputation performed. Ranges from 0 to 36 and higher numbers reflect better recall.	24 months
Secondary	Controlled Oral Word Association (COWA)	24 month estimated values Controlled Oral Word Association (COWA) by group. Linear model adjusts for baseline value and group assignment. No missing imputation performed. The COWA uses the three letter set of C, F, and L to assess phonemic fluency. Individuals are given 1 min to name as many words as possible beginning with one of the letters. The procedure is then repeated for the remaining two letters. Ranges from 0 to the total number of correct words that begin with one of the letters in the set. There is no ceiling of a maximum score. Higher numbers reflect better verbal fluency.	24 months
Secondary	Patient-reported Outcomes Measurement (PROMIS) Questionnaire - Applied Cognition - General Concerns - Short Form 4a	Patient reported quality of life outcomes obtained from patient-reported outcomes measurement (PROMIS) questionnaire - Applied Cognition - General Concerns - Short Form 4a . Scores range from 4-20 and then adjusted by t-scores ranging from 30.1-63.8. Higher scores reflect better cognition. Linear models include baseline assessment and group and multiple imputation was utilized.	24 months
Secondary	Patient-reported Outcomes Measurement (PROMIS) Questionnaire - Fatigue Short Form 41	Patient reported quality of life outcomes obtained from patient-reported outcomes measurement (PROMIS) questionnaire - Fatigue Short Form 41. Scores range from 4-20 and then adjusted by t-scores ranging from 33.7-75.8. Higher scores reflect worse fatigue. Linear models include baseline assessment and group and multiple imputation was utilized.	24 months