Statins for Reduction of Cardiac Toxicity in Patients Receiving HER2 Targeted

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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STACIE: Statins for Reduction of Cardiac Toxicity in Patients Receiving HER2 Targeted Therapy

Conditions
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Cardiac Toxicity, Early-stage Breast Cancer

Intervention / Treatment
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* Drug: Lipitor 40mg Tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Stage I-III HER2positive breast cancer receiving anti-HER2 therapy. Participants will receive Lipitor 40 mg PO daily. Anti-HER2 targeted therapy + Lipitor 40mg daily
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anti-HER2 targeted therapy + Lipitor 40mg daily<br>Participants will receive Lipitor 40 mg PO daily while receiving anti-HER2 therapy. | Drug: Lipitor 40mg Tablet<br>* LIPITOR® (atorvastatin calcium) tablets will be administered orally as a single dose of 40 mg once daily, with or without food<br>* Other names: Atorvastatin Calcium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With at Least One Adverse Event will be measured using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 for five years | Adverse events (AEs) will be measured using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 for five years | Five years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient reported outcome (PRO) for pain measured by the quality of Life questionnaire using PROMIS to measure pain | Quality of Life questionnaire using PROMIS will be administered at baseline, six, twelve and fifteen months | Baseline, six, twelve and fifteen months |