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.