statins for reduction of cardiac toxicity in patients receiving her2 targeted

Conditions: Cardiac Toxicity; Early-stage Breast Cancer

Summary: this study proposes that the addition of statins reduces the treatment delays or early discontinuations secondary to cardiotoxicity in patients with stage i-iii her2 positive breast being treated with anti-her2 therapy.

a single arm open-label phase 2 study to evaluate the cardioprotective effects of statins in patients with stage i-iii her2 positive breast cancer receiving her2 targeted therapy. this study will evaluate the hypothesis that addition of statins will reduce treatment delays/discontinuations related to symptomatic/asymptomatic cardiac dysfunction in patients being treated with anti-her2 therapy. the long-term goal of this study is to improve disease related outcomes and quality of life measures in patients being treated with anti-her2 therapy.

Eligibility criteria:
inclusion criteria: * histologically and/or cytologically confirmed diagnosis of stage i-iii female breast cancer (including inflammatory breast cancer) * scheduled to receive neoadjuvant/adjuvant her2 targeted therapy * between ≥18 years of age * female patients of childbearing potential must have a negative pregnancy test (serum or urine) prior to enrollment. female patients must agree to use effective barrier contraception during the period of therapy * baseline lvef ≥ 50% * prior cancers allowed if no evidence of disease in last 5 years * ecog 0-2 * no prior history of treatment with her2 targeted therapy or anthracyclines based chemotherapy * adequate bone marrow function: i. anc ≥ 1000/ul ii. platelet count ≥ 100,000/ul iii. hemoglobin ≥ 9.0 g/dl • adequate hepatic function: i. total bilirubin ≤ 1.5 x uln ii. ast (sgot) ≤ 5 x uln iii. alt (sgpt) ≤ 5 x uln * adequate renal function, creatinine \< 1.5x institutional uln or calculated creatinine clearance ≥ 50 ml/min as estimated using the cockcroft-gault formula * ability to understand the nature of this study protocol and give written informed consent * willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures exclusion criteria: * participants with stage iv breast cancer * participants currently taking statins * uncontrolled hypertension (systolic blood pressure \>190 mm hg or diastolic blood pressure \>100 mm hg) * no active liver disease * current use of cyp 3a4 inhibitors * any condition including the presence of laboratory abnormalities, which, in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study * life expectancy \< 12 weeks * pregnancy (positive pregnancy test) or lactation * pre-existing sensory neuropathy \> grade one * has significant cardiovascular disease, such as: lvef \< 50% at baseline as assessed by echo (preferred) i) class iii or class iv myocardial disease as described by the new york heart association ii) recent history (within 6 months prior to enrollment) of myocardial infarction; or iii) symptomatic arrhythmia at the time of randomization * major surgery without complete recovery in the past four weeks prior to screening * concurrent active infection * participant with uncontrolled and/ or active infection with hiv, hepatitis b or hepatitis c * participant who has a history of allergy or hypersensitivity to any of the study drugs * participant with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, interstitial pulmonary fibrosis, pulmonary hypersensitivity pneumonitis * any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study