Atorvastatin Calcium in Preventing Cardiovascular Complications in Patients with Newly Diagnosed Stage I-III Breast Cancer or Stage I-IV Lymphoma Undergoing Anthracycline-Based Chemotherapy
This randomized phase II/III trial studies atorvastatin calcium in preventing cardiovascular complications in patients with newly diagnosed stage I-III breast cancer or stage I-IV lymphoma undergoing anthracycline-based chemotherapy. Atorvastatin calcium may help prevent cardiovascular complications caused by drugs used in chemotherapy.
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 chemotherapy with an anthracycline (doxorubicin [doxorubicin hydrochloride] or epirubicin [epirubicin hydrochloride])
- Patients that are receiving or have received chemotherapy regimens are allowed
- Prior administration of anthracyclines is acceptable if therapy was completed > 6 months prior to study enrollment
- Able to hold breathe for 10 seconds
- Eastern Cooperative Oncology Group (ECOG) 0 or 1
- Patients with breast implants are usually permitted to have an magnetic resonance imaging (MRI); check with the MRI technician to confirm
- It is recommended the lipid profile be drawn fasting >= 8 hrs; serum lipid profile: total cholesterol/high-density lipoprotein (HDL)/low-density lipoprotein (LDL)/triglycerides (LDL levels prior to chemotherapy must be =< 190 mg/dl), within 30 days prior to enrollment * If labs are drawn non-fasting and LDL levels are >= 190 mg/dl the lipid profile should be repeated fasting to determine eligibility
- Alanine aminotransferase level (ALT) =< 3 x the upper limit of normal (ULN), within 30 days prior to enrollment
- Aspartate aminotransferase level (AST) =< 3 x ULN, within 30 days prior to enrollment
- Total bilirubin =< 2.0, within 30 days prior to enrollment
- Thyroid stimulating hormone (TSH) =< 1.5 times ULN, within 30 days prior to enrollment
- Creatinine kinase =< 2.5 x the ULN, within 30 days prior to enrollment
- It is recommended glucose be drawn fasting >= 8 hrs; glucose < 126 (diabetics 40–75 years of age are not eligible), within 30 days prior to enrollment * If glucose is >= 126 the glucose should be repeated fasting to determine eligibility
Exclusion Criteria
- Atherosclerotic cardiovascular disease (ASCVD) defined by history of acute coronary syndromes, myocardial infarction (MI), stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral arterial disease presumed to be of atherosclerotic origin
- 40 to 75 years of age with diabetes per American College of Cardiology (ACC)/American Heart Association (AHA) ACC/AHA 2013 guidelines
- Significant ventricular arrhythmias (> 20 premature ventricular contractions [PVCs]/min due to gating difficulty) atrial fibrillation with uncontrolled ventricular response
- Current use of statin therapy
- Current or history of hepatic dysfunction
- Uncontrolled hypothyroidism
- Recent extended history of constant-recurrent substance abuse 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
- Current use of the following cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP 3A4) inhibitors are not allowed: boceprevir, clarithromycin, cyclosporine (oral), darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir, gemfibrozil, grapefruit juice > 1 liter per day, itraconazole, lopinavir plus ritonavir, nelfinavir, saquinavir plus ritonavir, telaprevir, tipranavir plus ritonavir
- Current use of rifampin and digoxin
- Unable to provide informed consent
- Symptomatic claustrophobia
- Pregnant or breast feeding; women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence [not having sex], oral contraceptives, intrauterine device [IUD], Depo-Provera, tubal ligation, or vasectomy of the partner [with confirmed negative sperm counts] in a monogamous relationship [same partner]); an acceptable, although less reliable method involves the careful use of condoms and spermicidal foam or gel and/or cervical cap or sponge prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately; women who are currently breast-feeding are not eligible for this study
- Breast patients with tissue expanders are not allowed with the exception of tissue expanders made of material that are MRI compatible; check with the MRI technician to confirm
Additional locations may be listed on ClinicalTrials.gov for NCT01988571.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To determine if atorvastatin (atorvastatin calcium) administration preserves left ventricular ejection fraction (LVEF) 24 months after initiation of anthracycline-based chemo-therapy for breast cancer or lymphoma.
II. To determine if baseline to 6-month differences in LVEF predict baseline to 24-month differences in LVEF after anthracycline-based chemo-therapy and concomitant atorvastatin therapy.
SECONDARY OBJECTIVES:
I. To document the effect of atorvastatin on cognitive function using a battery of neurocognitive tests (Hopkins Verbal Learning Test [HVLT], Rey-Osterreith Figure, Controlled Oral Word Association [COWA], Trail-making Parts A and B, Digit Span and Grooved Pegboard) in breast cancer and lymphoma patients receiving an anthracycline.
II. To document the effect of atorvastatin on self-reported quality of life using validated questionnaires (Patient Reported Outcomes Measurement Information System [PROMIS] including: General form, Cognitive [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.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive atorvastatin calcium orally (PO) once daily (QD) for 24 months.
ARM II: Patients receive placebo PO QD for 24 months.
After completion of study treatment, patients are followed up for 30 days.
Trial PhasePhase II/III
Trial Typeprevention
Lead OrganizationWake Forest NCORP Research Base
Principal InvestigatorWilliam Gregory Hundley
- Primary ID98213
- Secondary IDsNCI-2013-01760, WF-98213, 00024197, CCCWFU 98213, WF 98213, WFU 98213, WFU-98213
- ClinicalTrials.gov IDNCT01988571