Cardiac Safety Study in Patients With HER2 + Breast Cancer

Title: A pilot study evaluating the cardiac safety of HER2 targeted therapy (non-lapatinib) in patients with HER2 positive breast cancer and reduced left ventricular function Phase: Pilot study Study Duration: 4 years with up to 5 additional years of follow up Study Center(s): 3 centers will be participating: MedStar Washington Hospital Center (MWHC), MedStar Georgetown University Hospital (MGUH) and Memorial Sloan Kettering Cancer Center (MSKCC) Primary Objective: To evaluate the cardiac safety of HER2 targeted therapy (non-lapatinib) in patients with HER2 positive breast cancer and reduced left ventricular ejection fraction (LVEF) when given concomitantly with cardiac treatment.

Secondary Objectives:

• To evaluate time to development of cardiac event or asymptomatic worsening of cardiac function
• Absolute changes in LVEF
• Delays in HER2 therapy attributed to cardiac causes
• Correlations between echocardiographic myocardial strain
• cTnI and hs-cTnT at baseline and over time with cardiac events and asymptomatic worsening of cardiac function Sample size: 30 patients

Diagnosis and Main Inclusion Criteria:

• HER2 positive breast cancer, stage I-IV.
• Mildly decreased cardiac function (LVEF between 40 and 49%) prior to or while receiving non-lapatinib HER2 targeted therapy

Cardiac Intervention:

• Beta-blockers and ACE-inhibitors titrated to the maximum tolerated doses

Oncology study Products, Doses, Routes, Regimens:

• Trastuzumab: loading dose of 8 mg/kg IV, followed by a maintenance dose of 6 mg/kg every 3 weeks, or a loading dose of 4 mg/kg followed by a maintenance dose of 2 mg/kg every week.
• Pertuzumab: loading dose of 840 mg IV, followed by 420 mg IV every 3 weeks, administered concomitantly with trastuzumab.
• Ado-trastuzumab emtansine: 3.6mg/kg IV every three weeks. Note: both trastuzumab and pertuzumab may be administered alone or in combination with other systemic or radiation therapy.

Duration of drug administration: Maximum of 12 months.

Inclusion criteria

• Female or male patient diagnosed with stage I-IV breast cancer
• HER2 positive breast cancer, defined by immunohistochemical staining for HER2 protein of 3+ intensity and/or amplification of the HER2 gene on fluorescence in situ hybridization (FISH) ≥ 2.0 on breast specimen or biopsy of a metastatic site
• LVEF < 50% and ≥ 40% documented in echocardiogram done within the last 30 days
• HER2 therapy naïve or currently receiving non-lapatinib HER2 targeted therapy
• Patient receiving or planning to receive trastuzumab, trastuzumab with pertuzumab or ado-trastuzumab emtansine, for at least 3 months, alone or in combination with other systemic treatment or radiation
• Age ≥ 18 years
• Patient is willing and able to comply with protocol required assessments and procedures

Exclusion criteria

• Previous hospitalization due to documented heart failure in the last 12 months
• Current signs or symptoms of heart failure or ischemia
• History of arrhythmia requiring pharmacological or electrical treatment
• Concomitant use of anthracyclines or use of anthracyclines in the last 50 days
• Pregnant or lactating patients. Patients of childbearing potential must implement contraceptive measures during study treatment and for 7 months after last dose of treatment drug and must have negative urine or serum pregnancy test within 7 days prior to registration.
• History of significant neurologic or psychiatric disorders including psychotic disorders or dementia that would prohibit the understanding and giving of informed consent.