Clinical trial NCT01988571: Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)
Official title: Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lymphoma
Keywords: Stage I breast cancer
Stage II breast cancer
Stage III breast cancer
Stage I Lymphoma
Stage II Lymphoma
Stage III Lymphoma
Stage IV Lymphoma
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2013-11-20
Enrollment: 279
Sex: ALL
Minimum age (years): 21
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: 24 months
Secondary outcomes:
measure: End Diastolic Volume
timeFrame: 24 months
measure: End Systolic Volume
timeFrame: 24 months
measure: Stroke Volume
timeFrame: 24 months
measure: Left Ventricular (LV) Mass
timeFrame: 24 months
measure: Pulse Wave Velocity
timeFrame: 24 months
measure: Hopkins Verbal Learning Test (HVLT) Total Recall
timeFrame: 24 months
measure: Controlled Oral Word Association (COWA)
timeFrame: 24 months
measure: Patient-reported Outcomes Measurement (PROMIS) Questionnaire - Applied Cognition - General Concerns - Short Form 4a
timeFrame: 24 months
measure: Patient-reported Outcomes Measurement (PROMIS) Questionnaire - Fatigue Short Form 41
timeFrame: 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Wichita
country: United States
facility: Cancer Center of Kansas-Wichita Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas - Wichita
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Medical Center Jefferson
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: Spectrum Health at Butterworth Campus
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital-Royal Oak
state: Michigan
city: Troy
country: United States
facility: William Beaumont Hospital - Troy
state: Michigan
city: Maplewood
country: United States
facility: Saint John's Hospital - Healtheast
state: Minnesota
city: Minneapolis
country: United States
facility: Abbott-Northwestern Hospital
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Clinic - Saint Louis Park
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Asheville
country: United States
facility: Mission Hospital
state: North Carolina
city: Asheville
country: United States
facility: Hope Women's Cancer Centers-Asheville
state: North Carolina
city: Burlington
country: United States
facility: Cone Health Cancer Center at Alamance Regional
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center
state: North Carolina
city: Charlotte
country: United States
facility: Oncology Specialists of Charlotte
state: North Carolina
city: Greensboro
country: United States
facility: Cone Health Cancer Center
state: North Carolina
city: Huntersville
country: United States
facility: Novant Health Cancer Institute - Huntersville
state: North Carolina
city: Huntersville
country: United States
facility: Southern Oncology Specialists-Huntersville
state: North Carolina
city: Kernersville
country: United States
facility: Novant Health Cancer Institute - Kernersville
state: North Carolina
city: Matthews
country: United States
facility: Novant Health Cancer Specialists-Matthews
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Forsyth Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Oncology Specialists
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Columbus
country: United States
facility: Columbus Oncology and Hematology Associates Inc
state: Ohio
city: Columbus
country: United States
facility: Doctors Hospital
state: Ohio
city: Delaware
country: United States
facility: Delaware Health Center-Grady Cancer Center
state: Ohio
city: Zanesville
country: United States
facility: Genesis Healthcare System Cancer Care Center
state: Ohio
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania/Abramson Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Easley
country: United States
facility: Prisma Health Cancer Institute - Easley
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Butternut
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Faris
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Eastside
state: South Carolina
city: Seneca
country: United States
facility: Prisma Health Cancer Institute - Seneca
state: South Carolina
city: Lynchburg
country: United States
facility: Centra Lynchburg Hematology-Oncology Clinic Inc
state: Virginia
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
city: Winchester
country: United States
facility: Shenandoah Oncology PC
state: Virginia
city: Burlington
country: United States
facility: Aurora Cancer Care-Southern Lakes VLCC
state: Wisconsin
city: Grafton
country: United States
facility: Aurora Cancer Care-Grafton
state: Wisconsin
city: Oshkosh
country: United States
facility: Vince Lombardi Cancer Clinic - Oshkosh
state: Wisconsin
city: Summit
country: United States
facility: Aurora Medical Center in Summit
state: Wisconsin
Study officials:
affiliation: Wake Forest University Health Sciences
name: Gregory Hundley, MD
role: PRINCIPAL_INVESTIGATOR
References: