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Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)

This study is currently recruiting participants.
Verified April 2017 by Wake Forest University Health Sciences
Sponsor:
ClinicalTrials.gov Identifier:
NCT01988571
First Posted: November 20, 2013
Last Update Posted: May 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Wake Forest University Health Sciences
  Purpose
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 Intervention Phase
Breast Cancer Drug: Atorvastatin Drug: Placebo Phase 2

Study Type: Interventional
Study Design: 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)

Resource links provided by NLM:


Further study details as provided by Wake Forest University Health Sciences:

Primary Outcome Measures:
  • 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:
  • 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.

  • 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.


Estimated Enrollment: 250
Actual Study Start Date: February 2014
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Information from the National Library of Medicine

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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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01988571


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         
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

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 Submitted: November 1, 2013
First Posted: November 20, 2013
Last Update Posted: May 30, 2017
Last Verified: April 2017

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