Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)
- Registration Number
- NCT01988571
- Lead Sponsor
- Wake Forest University Health Sciences
- Brief 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.
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 279
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2 - Placebo Placebo One placebo tablet each morning by mouth for 24 months. Arm 1 - Atorvastatin Atorvastatin One 40 mg Atorvastatin tablet each morning by mouth for 24 months Arm 2 - Placebo Atorvastatin One placebo tablet each morning by mouth for 24 months.
- Primary Outcome Measures
Name Time Method Left Ventricular Ejection Fraction (LVEF) 24 months 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.
- Secondary Outcome Measures
Name Time Method Left Ventricular (LV) Mass 24 months 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.
Hopkins Verbal Learning Test (HVLT) Total Recall 24 months 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.
End Diastolic Volume 24 months 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.
End Systolic Volume 24 months 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.
Pulse Wave Velocity 24 months 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.
Patient-reported Outcomes Measurement (PROMIS) Questionnaire - Fatigue Short Form 41 24 months 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.
Stroke Volume 24 months 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.
Controlled Oral Word Association (COWA) 24 months 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.
Patient-reported Outcomes Measurement (PROMIS) Questionnaire - Applied Cognition - General Concerns - Short Form 4a 24 months 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.
Trial Locations
- Locations (51)
Mission Hospital
🇺🇸Asheville, North Carolina, United States
Hope Women's Cancer Centers-Asheville
🇺🇸Asheville, North Carolina, United States
Novant Health Cancer Specialists-Matthews
🇺🇸Matthews, North Carolina, United States
Novant Health Presbyterian Medical Center
🇺🇸Charlotte, North Carolina, United States
Delaware Health Center-Grady Cancer Center
🇺🇸Delaware, Ohio, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Saint John's Hospital - Healtheast
🇺🇸Maplewood, Minnesota, United States
William Beaumont Hospital-Royal Oak
🇺🇸Royal Oak, Michigan, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Novant Health Cancer Institute - Huntersville
🇺🇸Huntersville, North Carolina, United States
Virginia Cancer Institute
🇺🇸Richmond, Virginia, United States
Prisma Health Cancer Institute - Faris
🇺🇸Greenville, South Carolina, United States
Centra Lynchburg Hematology-Oncology Clinic Inc
🇺🇸Lynchburg, Virginia, United States
Oncology Specialists of Charlotte
🇺🇸Charlotte, North Carolina, United States
Cone Health Cancer Center at Alamance Regional
🇺🇸Burlington, North Carolina, United States
Aurora Cancer Care-Southern Lakes VLCC
🇺🇸Burlington, Wisconsin, United States
Aurora Cancer Care-Grafton
🇺🇸Grafton, Wisconsin, United States
Novant Health Cancer Institute - Kernersville
🇺🇸Kernersville, North Carolina, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, 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
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
William Beaumont Hospital - Troy
🇺🇸Troy, Michigan, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
Cone Health Cancer Center
🇺🇸Greensboro, North Carolina, United States
University of Pennsylvania/Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Doctors Hospital
🇺🇸Columbus, Ohio, United States
Cancer Center of Kansas-Wichita Medical Arts Tower
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas - Wichita
🇺🇸Wichita, Kansas, United States
Vince Lombardi Cancer Clinic - Oshkosh
🇺🇸Oshkosh, Wisconsin, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Prisma Health Cancer Institute - Easley
🇺🇸Easley, South Carolina, United States
Prisma Health Cancer Institute - Eastside
🇺🇸Greenville, South Carolina, United States
Prisma Health Cancer Institute - Seneca
🇺🇸Seneca, South Carolina, United States
Aurora Medical Center in Summit
🇺🇸Summit, Wisconsin, United States
Spectrum Health at Butterworth Campus
🇺🇸Grand Rapids, Michigan, United States
Southern Oncology Specialists-Huntersville
🇺🇸Huntersville, North Carolina, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Novant Health Forsyth Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Novant Health Oncology Specialists
🇺🇸Winston-Salem, North Carolina, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Ochsner Medical Center Jefferson
🇺🇸New Orleans, Louisiana, United States
Prisma Health Cancer Institute - Butternut
🇺🇸Greenville, South Carolina, United States
Shenandoah Oncology PC
🇺🇸Winchester, Virginia, United States
Genesis Healthcare System Cancer Care Center
🇺🇸Zanesville, Ohio, United States