This phase I trial studies the side effects and best dose of a vaccine therapy in preventing cancer from coming back in patients with non-metastatic, node positive, human epidermal growth factor receptor (HER)2 negative breast cancer in which all signs and symptoms have disappeared. Vaccines made from deoxyribonucleic acid (DNA) may help the body build an effective immune response to kill tumor cells. Giving multiple vaccinations may make a stronger immune response and prevent or delay the return of cancer.
OUTLINE: This is a dose escalation study of WOKVAC. Patients receive WOKVAC with sargramostim intradermally (ID) on day 1. Courses repeat every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients with axillary lymph node dissection (ALND) will have vaccine administered to the contralateral arm. Patients with bilateral ALND will have vaccine administered in the thigh. As much as possible each vaccine dose will be given within the same draining lymph node site. Patients will be monitored for a minimum of 60 minutes post vaccine administration. After completion of study treatment, patients are followed up at 1 month, 6 months and annually for up to 5 years thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
32
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
Number of Adverse Events Per Common Terminology Criteria for Adverse Events Version 4.0
Toxicities by grade that were related (possibly, probably or definitely) to the study vaccine noted during the immunization regimen will be summarized. This is done by arm, Grade and Attribution to study vaccine.
Time frame: Up to 9 months
Assessment of IgG Antibodies
Immune response will be measured by indirect enzyme-linked immunosorbent assay and serum antibody avidity to determine an avidity index before and after vaccination. Patients will be considered to have developed an antibody response if antigen specific IgG antibodies are both detectable and have moderate to high avidity.
Time frame: Up to 4 months
Assessment of T Helper Th1:Th2 Ratio
IFN-g (Th1) and IL-10 (Th2) T-cells will be evaluated using enzyme-linked immunosorbent spot assay. Patients will be considered to have developed a Th1 immune response as the sum IFN-Ɣ magnitude from all antigens to maximum response. This will be presented as a median fold change from baseline to the maximum response (1 or 6 months after vaccination).
Time frame: Up to 9 months
Assessment of the Immunogenicity of WOKVAC by Generation of IGFBP-2, HER2, and IGF-1R Specific Type 1 (Th1) T- Cells
Immune responses will be measured by IFN-g enzyme-linked immunosorbent spot assay using blood (PBMC) represented by a maximum immune response generated to each antigen individually measured as corrected spots per well (cSPW). At the immune evaluations, each patient was given a value to indicate their immune response at both baseline and post vaccination. This data is represented by a median response, at both baseline (before vaccination) and 1 month or 6 months after the last vaccination of 3 vaccines (maximum response), to each of the 3 vaccine antigens HER2, IGFBP-2 or IGF1R.
Time frame: Up to 24 weeks
Level of Antigen Specific Central and Effector Memory Phenotypes (Persistent Memory T Cell Response)
Assessed by flow cytometry of peripheral blood mononuclear cells using an established T-cell activation panel and summarized with mean and standard deviation or median and range over time.
Time frame: Up to 6 months after the last vaccine
Modulation of Myeloid Derived Suppressor Cell Levels
Assessed by flow cytometry of peripheral blood mononuclear cells using an established myeloid derived suppressor cell/ regulatory T-cell panel and summarized with mean and standard deviation or median and range over time.
Time frame: Up to 24 weeks
Modulation of T Regulatory Cell Levels
Assessed by flow cytometry of peripheral blood mononuclear cells using an established myeloid derived suppressor cell/ regulatory T-cell panel and summarized with median and range. FOXP3 is used to identify regulatory T cells, specifically CD4+ cells isolated from PBMC.
Time frame: Up to 24 weeks
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