Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)
Condition: Breast Cancer; Lymphoma
MeSH terms: Lymphoma; Breast Neoplasms
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Atorvastatin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 40 mg tablet taken by mouth each morning for 24 months.; One placebo tablet taken each morning orally for 24 months.
Other intervention name(s): Lipitor; sugar pill
Intervention MeSH terms: Atorvastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
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