Vaccine Therapy, Trastuzumab, and Vinorelbine in Treating Patients With Locally Recurrent or Metastatic Breast Cancer

OBJECTIVES:

Primary

- Determine the efficacy of multiepitope autologous dendritic cell vaccine in combination
with trastuzumab (Herceptin®) and vinorelbine ditartrate in patients with locally
recurrent or metastatic breast cancer whose tumors overexpress human epidermal growth
factor receptor 2 (HER2/neu).

Secondary

- Determine if this regimen is effective in generating functional antigen-specific T
cells.

OUTLINE:

- Therapeutic autologous dendritic cell (DC) preparation: Patients undergo mobilization of
DC and apheresis for production of therapeutic DC. DCs are expanded in vitro for 10-20
days and pulsed with E75 and E90 peptides.

- Treatment: Patients receive vinorelbine ditartrate IV over 6-10 minutes, therapeutic
autologous DC intradermally over 2-5 minutes, and trastuzumab (Herceptin®) IV over 30-90
minutes on day 1. Patients receive sargramostim (GM-CSF) subcutaneously on days 2, 4,
and 6, or until neutrophil counts recover. Treatment repeats every 14 days for up to 6
courses (or more at the discretion of the investigator) in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months.

PATIENT ELIGIBILITY

4.1 Inclusion Criteria 4.1.1 Histologically proven metastatic breast cancer with measurable
or evaluable disease per investigator discretion.

4.1.2 Patients must be 18 years of age or older. Women of child bearing potential must be
practicing barrier or oral contraception for the duration of the study, or documented as
surgically sterile or one year post-menopausal.

4.1.3 Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (See Appendix A).

4.1.5 Cardiac function by multigated acquisition scan (MUGA) with an ejection fraction (EF)
> 45% or an echocardiogram that shows normal left ventricle (LV) function.

4.1.6 Serum Creatinine < 2.0 mg/dl. 4.1.7 Hepatic transaminases (alanine aminotransferase
(ALT) and aspartate aminotransferase (AST)) ≤3.0 times the upper limit of normal if no
liver metastases or ≤5 times the upper limit of normal if liver metastases are present.

4.1.8 Bilirubin no more than 2 times normal.

4.1.9 Seronegative for HIV.

4.1.10 Negative for Hepatitis B surface antigen.

4.1.11 Signed and dated informed consent.

4.1.12 HLA A0201+ by DNA genotyping.

4.1.13 Absolute neutrophil count greater than 1,500/mm3. Platelet count greater 100,000/mm3
and hemoglobin greater than or equal to 10

4.1.14. 3+ expression of HER-2/neu from original pathology (diagnostic) tumor sample by
Immunohistochemistry (IHC) or 2+ expression by IHC with gene amplification by fluorescence
in situ hybridization (FISH).

4.1.15. Patients will be eligible even if they have failed treatment for metastatic breast
cancer with trastuzumab and a chemotherapy agent other than vinorelbine or if they have
progressed within 12 months of receiving adjuvant chemotherapy using trastuzumab and a
taxane.

4.2 Exclusion Criteria

4.2.1 Patients with any serious medical, cardiac, or psychiatric condition which, in the
opinion of the investigator, would make the patient unsuitable for study participation or
would impede probable compliance with the protocol.

4.2.2 Patients with central nervous system metastases must have stable disease for at least
3 months prior to study entry.

4.2.3 Patient is currently taking steroid medications. Systemic steroid treatment is not
allowed.

4.2.4 Patients that have failed prior therapy with vinorelbine + trastuzumab will not be
eligible for therapy.

4.2.5 Patient has received hormonal or cytotoxic chemotherapy within 14 days of apheresis
and within 28-30 days prior to study treatment.