A Randomized, Open-Label Comparative Study of Combination Therapy With Cyclophosphamide and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine With or Without Trastuzumab for the Treatment of Metastatic Breast Cancer That Does NOT Over-express HER-2/Neu
- To evaluate the safety of cyclophosphamide-modulated vaccination with vs without
trastuzumab in patients with breast cancer that does not overexpress HER-2/neu.
- To compare the clinical benefit of cyclophosphamide-modulated vaccination with vs
without trastuzumab in these patients.
- To measure HER-2/neu-specific CD4+ and CD8+ T-cell immunity by delayed-type
hypersensitivity (DTH) and ELISPOT.
- To measure the pharmacodynamics of CD4+CD25+ regulatory T cells by flow cytometry.
- To assess the impact of trastuzumab on immune priming in vivo by immunohistochemistry
of vaccine-site biopsies at day +3 and day +7 of courses 1 and 3 on the two study arms,
comparing cellular infiltrates to those seen in previous preclinical and clinical
- To measure hTERT-specific CD8+ T-cell immunity by ELISPOT.
- To characterize the peripheral-memory T-cell pool.
- To determine baseline and change in vaccine site-draining lymph node immunohistology
and gene expression profile.
- To develop the tandem tetramer/CD107a cytotoxicity assay for HER-2/neu-specific CD8+ T
- To measure novel T-cell responses induced by trastuzumab and cyclophosphamide-modulated
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic
GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6
weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Patients then receive a fourth vaccination at 6-8 months.
- Arm II: Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab
IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the
absence of disease progression or unacceptable toxicity. Patients then receive a fourth
vaccination at 6-8 months.
Skin punch and lymph node biopsies are collected at baseline and on days +3 and +7 of
courses 1 and 3 for biomarker analysis.
After completion of study treatment, patients are followed periodically.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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|