Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)

Study Description

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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 women receiving adjuvant anthracycline-based chemotherapy for breast cancer.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: Atorvastatin; Drug: Placebo	Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

Specific Aim 1:

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

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 250 women scheduled to receive Anthracycline-based adjuvant therapy for treatment of adjuvant breast cancer. We will use innovative noninvasive magnetic resonance imaging (MRI) procedures to accurately measure LVEF. In addition, we will measure 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 CHF evolve in women given Anthracycline-based adjuvant therapy for adjuvant breast cancer. These data will be useful to physicians trying to determine the optimal cardiac protection strategies when administering adjuvant chemotherapeutic regimens to their breast cancer patients. The objective of this research is to use inexpensive medications to preserve CV health and thereby improve overall survival in the growing number of breast cancer patients.

SECONDARY OBJECTIVES

Specific Aim 1:

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

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	250 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Prevention
Official Title:	Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)
Actual Study Start Date :	February 2014
Estimated Primary Completion Date :	October 2018
Estimated Study Completion Date :	October 2018

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: Arm 1 - Atorvastatin; One 40 mg Atorvastatin tablet each morning by mouth for 24 months	Drug: Atorvastatin; 40 mg tablet taken by mouth each morning for 24 months.; Other Name: Lipitor
Placebo Comparator: Arm 2 - Placebo; One placebo tablet each morning by mouth for 24 months.	Drug: Atorvastatin; 40 mg tablet taken by mouth each morning for 24 months.; Other Name: Lipitor Drug: Placebo; One placebo tablet taken each morning orally for 24 months.; Other Name: sugar pill

Outcome Measures

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Primary Outcome Measures :

1. Determine if Atorvastatin (Lipitor) administration preserves LV Function [ Time Frame: 24 months ]
   Clinical measurements obtained from Cardiac MRI Left Ventricular Ejection Fraction Left Ventricular Volume Strain Fibrosis Wall Thickness Pulse Wave Velocity

Secondary Outcome Measures :

1. Document the effect of atorvastatin on cognitive function [ Time Frame: 24 months ]
   Measured by the Controlled Oral Word Association Test, Hopkins Verbal Learning Test - revised, Trail Making Test (A and B), Rey-Osterrieth Complex Figure - modified, Digit Span Test and Grooved Pegboard.
2. Document effect of Atorvastatin on self-reported quality of life [ Time Frame: 24 months ]
   Patient reported quality of life outcomes obtained from PROMIS questionnaires. Cognitive concerns; Cognitive abilities; Fatigue; Mood; Pain Intensity and Interference; Sleep Disturbance and Physical Function.

Eligibility Criteria

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Ages Eligible for Study:	30 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Newly diagnosed Stage I-III female breast cancer (including inflammatory breast cancer)
• Scheduled to receive adjuvant chemotherapy with an Anthracycline (doxorubicin and epirubicin)
• 30 to 80 years of age
• LVEF > 50% (Most recent within the last 5 years)
• Prior chemotherapy regimen not containing anthracyclines is allowed
• Able to hold breath for 15 seconds
• Prior cancers allowed if no evidence of disease in last 5 years
• 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 PVCs/min due to gating difficulty) atrial fibrillation with uncontrolled ventricular response; coronary artery disease; acute myocardial infarction within 28 days
• Current use of CYP 3A4 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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Robin Rosdhal, RN	(336) 713-6519	rosdhal@wakehealth.edu

Locations

United States, North Carolina
Wake Forest Baptist Medical Center	Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Robin Rosdhal, RN 336-713-6519 rosdhal@wakehealth.edu
Principal Investigator: William G Hundley, MD
United States, Wisconsin
University of Wisconsin Carbon Cancer Center	Recruiting
Madison, Wisconsin, United States, 53792
Contact: Cindy Adams, RN 608-262-8158 supportiveoncology@uwcarbone.wisc.edu
Principal Investigator: Toby Campbell, MD

Sponsors and Collaborators

Wake Forest University Health Sciences

National Cancer Institute (NCI)

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:	Gregory Hundley, MD	Wake Forest University Health Sciences

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Wake Forest University Health Sciences
ClinicalTrials.gov Identifier:	NCT01988571 History of Changes
Other Study ID Numbers:	REBACCCWFU 98213; U10CA081851 ( U.S. NIH Grant/Contract ); 1R01HL118740-01 ( U.S. NIH Grant/Contract )
First Posted:	November 20, 2013
Last Update Posted:	February 20, 2018
Last Verified:	February 2018

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Wake Forest University Health Sciences:

Stage I breast cancer; Stage II breast cancer; Stage III breast cancer

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Atorvastatin Calcium; Anticholesteremic Agents	Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors