Detection and Prevention of Anthracycline-Related Cardiac Toxicity With Concurrent Simvastatin
Condition: Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Stage III Breast Cancer
MeSH terms: Breast Neoplasms; Cardiotoxicity
Intervention: Simvastatin; Doxorubicin/cyclophosphamide
Intervention description: Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily.; The standard chemotherapy regimen that must be planned for all participants in order to take part in this study. The regimen is given every 2 or 3 weeks per standard of care, at the direction of the treating physician.
Intervention MeSH terms: Cyclophosphamide; Doxorubicin; Simvastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast cancer; Adriamycin; Simvastatin; Statin; Echocardiogram

Summary:

      Doxorubicin (Adriamycin), one of the drugs commonly used for the treatment of breast cancer,
      is in a class of medications called anthracyclines. Anthracyclines may cause heart damage
      that can lead to weakening of the heart muscle. This heart damage may happen right away or
      may occur many years after the anthracycline is given

      Simvastatin is an oral medication approved by the FDA to lower cholesterol. Simvastatin is in
      a class of medications called statins. Some research has shown that statins may prevent heart
      damage that can be caused by anthracyclines like Doxorubicin (Adriamycin).

      The purpose of this study is to determine if taking simvastatin while receiving the
      chemotherapy Doxorubicin (Adriamycin) will minimize damage to the heart.

      This study is for women who will be receiving the anthracycline doxorubicin (Adriamycin) as
      part of their breast cancer treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female Sex (Note: Patients may be pre-menopausal or post-menopausal)

          -  Age 18 years or older

          -  Histologically confirmed invasive breast carcinoma, stage I-III (Note: Estrogen
             Receptor (ER), Progesterone Receptor (PR) and HER2 status must be known. In newly
             diagnosed patients planning neoadjuvant treatment, a formal assessment of axillary
             lymph nodes is not required.)

          -  Planning to initiate adjuvant or neoadjuvant AC (adriamycin and cytoxan) chemotherapy
             (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 2-3 weeks x 4 cycles).
             (Note: Participants may be planning to receive adjuvant taxane therapy after the
             completion of AC chemotherapy. HER2 positive patients must be planning to initiate
             trastuzumab therapy after AC chemotherapy.)

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Normal organ function and marrow function as defined by:

               -  Absolute neutrophil count (ANC) ≥ 1,000

               -  Platelet count ≥ 100,000

               -  Total bilirubin less than or equal to the upper limit of normal

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 times
                  the upper limit of normal

               -  Creatinine ≤1.5 times the upper limit of normal

               -  Creatine kinase (CK) ≤2.5 times the upper limit of normal

          -  Left ventricular ejection fraction (LVEF) as assessed by baseline echocardiogram at or
             above the lower limit of normal

          -  Women of childbearing potential must agree to use adequate contraception (non-hormonal
             or barrier method of birth control or abstinence) prior to study entry and for the
             duration of participation. Should a woman become pregnant or suspect she is pregnant
             while participating in the study, she should inform her treating physician immediately

          -  Ability to understand the study regimen and the willingness to sign a written informed
             consent document

          -  Negative pregnancy test (women of childbearing potential only)

        Exclusion Criteria:

          -  Prior anthracycline therapy

          -  Currently pregnant or lactating

          -  Currently receiving investigational agents

          -  Known active liver disease (cirrhosis, chronic viral hepatitis, autoimmune liver
             disease or other known clinically significant active liver disease)

          -  Known myopathy or history of rhabdomyolysis

          -  Uncontrolled hypothyroidism

          -  History of allergic reaction or intolerance to statin treatment

          -  Currently receiving statin therapy or have received any statin therapy within the last
             3 months

          -  Known history of ischemic cardiac disease (including angina requiring anti-anginal
             medications, myocardial infarction, coronary artery disease documented on cardiac
             catheterization or ischemia documented on stress test), congestive heart failure,
             clinically significant arrhythmia or conduction system abnormalities, clinically
             significant valvular disease, clinically significant pericardial effusion or EF below
             the lower limit of normal

          -  Uncontrolled inter-current illness including, but not limited to, ongoing or active
             serious infection, other active cardiac disease or psychiatric illness/social
             situations which would limit compliance with study requirements

          -  Inability to swallow tablets or use of a feeding tube

          -  Gastrointestinal disease, surgery or malabsorption that could potentially impact the
             absorption of the study drug

          -  Daily consumption of alcohol exceeding 3 standard drinks a day (defined as 10 grams of
             alcohol, which is equivalent to 285 mL of beer, 530 mL of light beer, 100 mL of wine
             or 30 mL of liquor)

          -  Women currently taking drugs which are strong inhibitors or inducers of CYP3A4 are not
             eligible. These may be found at the Indiana University Clinical Pharmacology website
             at http://medicine.iupui.edu/clinpharm/ddis/main-table/.

          -  Women taking associated with a substantial risk of myopathy when co-administered with
             simvastatin are not eligible. These drugs are listed in the simvastatin package insert
             (available at: http://www.merck.com/product/usa/pi_circulars/z/zocor/zocor_pi.pdf).

          -  Women taking medications for which interaction with simvastatin may result in
             increased levels are not eligible. Such drugs are listed in the simvastatin package
             insert (available at:
             http://www.merck.com/product/usa/pi_circulars/z/zocor/zocor_pi.pdf).

          -  Any medical condition which, in the opinion of the investigator, puts the patient at
             risk of potentially serious complications while on study treatment