Overview
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.
Description
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
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