Xenogeneic HER2/Neu DNA Immunization for Patients With Metastatic and High Risk Breast Cancer: A Phase I Study to Assess Safety and Immunogenicity

Breast cancer patients with AJCC Stage III or metastatic (AJCC Stage IV) disease that
over-express HER2 will potentially be eligible for this trial. Patients may have measurable
disease, evaluable disease or be without evidence of disease. They may be receiving
hormonal therapy and they may have already received trastuzumab (Herceptin) or be receiving
trastuzumab during this study.

Inclusion Criteria:

Patients must have ALL of the features listed below:

- AJCC Stage IV breast cancer (histologically confirmed) with no evidence of disease or
stable disease. Patients may be either off therapy or on hormone therapy and/or
trastuzumab.

OR AJCC Stage III breast cancer < or = to 36 months post completion of adjuvant therapy.

- Pathology slides must be reviewed by the Department of Pathology at MSKCC.

- HER2 over-expression by FISH or by staining 3+ on immunohistochemistry in either the
primary or metastatic tumor.

- Karnofsky performance status > or = to 80%.

- Patients must have recovered from the toxicity of any prior therapy, and not received
major surgery, radiation therapy, or chemotherapy for at least 4 weeks prior to entry
into the trial. (Ongoing hormonal therapy and/or trastuzumab administration is
permitted.)

- Age > 18 years

Exclusion Criteria:

- Pregnancy (Women of child bearing potential must not be pregnant and have a normal
pregnancy test within 2 weeks of starting treatment.) Woman who may yet bear children
and sexually active men must be using appropriate contraception during the course of
this study. Patients must be counseled not to become pregnant during the study.
Patients must also be counseled that injection of HER2 may have unknown affects on the
viability of a future fetus.

- Nursing

- Prior cumulative doxorubicin dose > 360 mg/m2

- Prior cumulative epirubicin dose > 600 mg/m2

- Other active cancers (within the prior five years, excluding non-melanoma skin
cancer).

- Inadequate organ function as defined by any of the following:

- total white blood cell count of < 3,000 cells/mm3

- platelet count < 100,000/mm3

- serum creatinine > 1.5 x upper limit of normal

- aspartate aminotransferase (AST) > 2 x the upper limit of normal

- History of cardiac disease as defined by any of the following:

- any prior myocardial infarction

- history of documented congestive heart failure

- left ventricular ejection fraction below the normal institutional range

- use of medications for treatment of angina pectoris

- any prior arrhythmia or cardiac valvular disease requiring medication or
clinically significant

- History of known immunodeficiency or autoimmune disease.

- Any use of medication (e.g., corticosteroids) which might make it difficult for the
patient to complete the full course of treatments or to respond immunologically to
vaccines is grounds for exclusion, at the discretion of the Principal Investigator or
co-Principal Investigators.

- Previous breast cancer vaccine exposure

- Active CNS or leptomeningeal tumor

- Active infection requiring antibiotic treatment

- Anticipated survival of less than 6 months