A Safety and Bioactivity Study of Combination Therapy With Trastuzumab, Cyclophosphamide, and an Allogeneic GM-CSF-Secreting Breast Tumor Vaccine for the Treatment of Patients With High Risk/ Metastatic HER-2/Neu- Overexpressing Breast Cancer With No Evidence of Disease
- To evaluate the safety of allogeneic sargramostim (GM-CSF)-secreting breast cancer
vaccine in combination with trastuzumab (Herceptin®) and cyclophosphamide in patients
with high-risk or metastatic HER2/neu-overexpressing breast cancer.
- To measure the HER2/neu-specific CD4+ T-cell response by delayed-type hypersensitivity.
- To measure the magnitude of HER2/neu-specific CD8+ T-cell responses by ELISPOT.
- To assess the impact of trastuzumab on immune priming in vivo by IHC.
- To measure the impact of cyclophosphamide pretreatment on CD4+CD25+ regulatory T cells
by flow cytometry.
- To determine the time to disease progression.
- To develop the tandem tetramer/CD107a cytotoxicity assay for HER2/neu-specific CD8+ T
- To measure novel T-cell responses induced by trastuzumab and cyclophosphamide-modulated
OUTLINE: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes once weekly
beginning on day -1 of the first course of vaccination and continuing until the completion
of the last course of vaccination. Patients also receive cyclophosphamide IV over 30 minutes
on day -1 and allogeneic sargramostim (GM-CSF)-secreting breast cancer vaccine intradermally
on day 0. Treatment with cyclophosphamide and the vaccine repeats every 27-42 days for up to
3 courses in the absence of disease progression or unacceptable toxicity. Patients then
receive a fourth course of cyclophosphamide and vaccine approximately 6-8 months after the
Patients undergo delayed-type hypersensitivity testing and blood sample collection at
baseline and periodically during study for immunologic laboratory studies. Blood samples are
analyzed for serum GM-CSF levels by pharmacokinetic studies and for immune monitoring by
ELISPOT and flow cytometry. Skin punch biopsies are also performed periodically and analyzed
After completion of study treatment, patients are followed periodically.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety (local and systemic toxicity) as assessed by NCI CTCAE v3.0
Leisha A. Emens, MD, PhD
Sidney Kimmel Comprehensive Cancer Center
United States: Food and Drug Administration
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|