Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Breast Neoplasms

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Breast Diseases

Skin Diseases

Lymphosarcoma

Lipid Regulating Agents

All Drugs and Chemicals

Atorvastatin

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Anticholesteremic Agents

Hypolipidemic Agents

Antimetabolites

Enzyme Inhibitors

One 40 mg Atorvastatin tablet each morning by mouth for 24 months

One placebo tablet each morning by mouth for 24 months.

40 mg tablet taken by mouth each morning for 24 months.

One placebo tablet taken each morning orally for 24 months.

Placebo

Gregory Hundley, MD

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.

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.

Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

National Cancer Institute (NCI)

National Heart, Lung, and Blood Institute (NHLBI)

Wake Forest University Health Sciences

Serious Adverse Event reporting begins after the informed consent is signed. Serious Adverse Events occurring within 30 days of study completion must be reported via FDA Form 3500 (MedWatch).

One 40 mg Atorvastatin tablet each morning by mouth for 24 months

Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months.

Arm 1 - Atorvastatin

One placebo tablet each morning by mouth for 24 months.

Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months.

Placebo: One placebo tablet taken each morning orally for 24 months.

Arm 2 - Placebo

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Number of participants on Medicare. Insurance categories are check all that apply, participants could report more than 1 insurance type.

Medicare

Number of participants on Medicaid. Insurance categories are check all that apply, participants could report more than 1 insurance type.

Medicaid

Number of participants on private health insurance. Insurance categories are check all that apply, participants could report more than 1 insurance type.

Private Insurance

Number of participants reporting having no health insurance

No Health Insurance

Defined as lymphoma or breast cancer (those were the only two types eligible for this trial).

Cancer Type

Clinical staging is based on the results of tests done before surgery, which may include physical examinations, ultrasound, and MRI scans. Cancer stages range from 1-4. The higher the number, the larger the cancer tumor and the more it has spread to nearby tissues. Stage 4 has spread to distant parts of the body. Higher stages are associated with worse prognosis.

Cancer Stage

Marital Status

Self reported highest level of education.

Education

Income

Job Status

Body Mass Index

Lead Biostatistician

Linear models adjusting for baseline values and utilized multiple imputation for missing data.

All those with baseline and 24 month cardiac MRI (multiple imputation utilized for missing data).

Left Ventricular Ejection Fraction (LVEF)

End Diastolic Volume

End Systolic Volume

Stroke Volume

Left Ventricular (LV) Mass

Pulse Wave Velocity

Those with data available at baseline and 24 months.

Hopkins Verbal Learning Test (HVLT) Total Recall

Controlled Oral Word Association (COWA)

Those with baseline and 24 month assessment completed. Multiple imputation was utilized for missing data.

Spots Global Cancer Trial Database for stage i lymphoma