Vaccine Therapy in Treating Patients With Stage IV Breast Cancer

PRIMARY OBJECTIVES:

I. To evaluate the safety of infusing escalating doses of HER2 specific T cells into
patients with advanced HER2+ breast cancer using ex vivo expanded autologous T cells.

SECONDARY OBJECTIVES:

I. To investigate to what extent HER2 specific T cell immunity can be boosted or generated
in individuals after infusion of HER2 specific T cells.

II. To evaluate how long T cell immune augmentation persists in vivo after adoptive transfer
of HER2 specific T cells and subsequent booster immunizations.

III. To determine the development of cluster of differentiation (CD)4+ and CD8+ epitope
spreading after adoptive transfer of HER2 specific T cells.

TERTIARY OBJECTIVES:

I. To investigate the potential anti-tumor effects of HER2 specific T cells in patients with
advanced HER2+ breast cancer.

II. To determine whether indium-labeled HER-2 specific T-cells traffic to sites of
metastatic disease once adoptively transferred using SPECT or SPECT-CT imaging.

III. To assess whether adoptively transferred HER-2 specific T-cells induce acute
inflammation at metastatic sites of disease by assessing the development of tumor
inflammation after the second or third infusion of cells using PET-CT imaging.

OUTLINE: This is a phase I/II, dose-escalation study of ex vivo-expanded HER2-specific
autologous T cells.

Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) intradermally
(ID) on days 1, 8, and 15. Beginning 2 weeks later, patients undergo leukapheresis to
isolate and collect peripheral blood mononuclear cells for T-cell expansion.

Patients receive cyclophosphamide intravenously (IV) once on day -1 and autologous ex
vivo-expanded HER2-specific T cell IV over 30 minutes on day 1. Treatment repeats every 7-10
days for up to three treatments. Patients receive a booster HER2/neu peptide vaccine 1 month
after the final T-cell infusion, followed by 2 additional booster vaccines at 2-month
intervals.

While on the study, patients may continue their standard-of-care (non-research) treatment
with trastuzumab and/or lapatinib IV weekly or every 3 weeks, except for 7 days before the
cyclophosphamide dose, treatment 1 and treatment 2 and at least 7 days after receiving the
second T cell vaccine. (Trastuzumab and lapatinib are not required or provided in this
study).

Before the third T cell treatment of HER2 specific T-cells we will label a small sample of
the patient's T-cells with indium-111. Prior to the final infusion of T-cells, patients will
have FDG PET-CT performed. This scan will be repeated 48 hours after T-cell infusion. In
addition, patients would then undergo SPECT or SPECT-CT imaging at 4, 24, 48, and 72 hours
(+/- 3 hours) after labeled cells have been infused.

After completion of study treatment, patients are followed up every 3 months for 1 year,
every 4 months for the following year, and then twice a year thereafter. This consists of
blood collection and contact with patients physician.

Inclusion Criteria:

- Patients with HER2+ Stage IV breast cancer that have been maximally treated and not
achieved a complete remission

- Patients must have stable or slowly progressive disease state, measurable disease as:

- Extraskeletal disease that can be accurately measured >= 10 mm by standard
imaging techniques that can include but not limited to computed tomography (CT),
positron emission tomography (PET), PET/CT, magnetic resonance imaging (MRI);

- Skeletal or bone-only disease which is measurable by fludeoxyglucose (FDG) PET
or PET/CT imaging will also be allowed

- Patients can be currently receiving trastuzumab and/or lapatinib and/or hormonal
therapy and/or bisphosphonate therapy

- HER2 overexpression in the primary tumor or metastasis by immunohistochemistry (IHC)
of 2+ or 3+, or documented gene amplification by fluorescence in situ hybridization
(FISH) analysis; if overexpression is 2+ by IHC, then patients must have HER2 gene
amplification documented by FISH

- Subjects must have a Performance Status Score (Southwest Oncology Group [SWOG]/Zubrod
Scale) = 0, 1 or 2

- Patients must be off all immunosuppressive treatments such as chemotherapy or
systemic steroid therapy a minimum of 14 days prior to initiation of study (i.e.
first vaccination)

- Patients on trastuzumab and/or lapatinib must have a baseline left ventricular
ejection fraction (LVEF) measured by multi gated acquisition scan (MUGA) or
echocardiogram (ECHO) equal to or greater than the lower limit of normal for the
facility within 90 days of eligibility determination

- Men and women of reproductive ability must agree to contraceptive use during the
entire study period

- Patients must have an expected survival of 6 months

- White blood cell (WBC) >= 3000/mm^3

- Absolute neutrophil count (ANC) >= 1000/mm^3

- Hemoglobin (Hgb) >= 10 mg/dl

- Platelets >= 75,000/mm^3

- Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min

- Total bilirubin =< 2.5 mg/dl

- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =< 3
times upper limit of normal (ULN)

- Patients must be >= 18 years old

Exclusion Criteria:

- Patients with any of the following cardiac conditions:

- Symptomatic restrictive cardiomyopathy;

- Unstable angina within 4 months prior to enrollment;

- New York Heart Association functional class III-IV heart failure on active
treatment

- Patients with any contraindication to receiving rhuGM-CSF based products

- Patients with any clinically significant autoimmune disease uncontrolled with
treatment

- Patients with a history of brain metastases must have a stable head imaging study
within 30 days of eligibility determination; specifically, patients with active brain
metastases will not be eligible for study

- Patients who are simultaneously enrolled in any other treatment study

- Pregnant or breast-feeding women