A Phase I Trial of the Safety and Immunogenicity of a DNA Plasmid Based Vaccine (WOKVAC) Encoding Epitopes Derived From Three Breast Cancer Antigens (IGFBP-2, HER2, and IGF-1R) in Patients With Breast Cancer
Overview
- Phase
- Phase 1
- Intervention
- Laboratory Biomarker Analysis
- Conditions
- HER2/Neu Negative
- Sponsor
- University of Washington
- Enrollment
- 24
- Locations
- 2
- Primary Endpoint
- Number of Adverse Events Per Common Terminology Criteria for Adverse Events Version 4.0
- Status
- Active, Not Recruiting
- Last Updated
- 4 years ago
Overview
Brief Summary
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.
Detailed Description
PRIMARY OBJECTIVES: I. To assess the safety of 3 escalating doses of a deoxyribonucleic acid (DNA) plasmid based vaccine encoding three breast cancer antigens (insulin-like growth factor-binding protein \[IGFBP\]-2, HER2, and insulin-like growth factor \[IGF\]-1 receptor \[1R\]) in patients with breast cancer. SECONDARY OBJECTIVES: I. To determine the immunogenicity of pUMVC3-IGFBP2-HER2-IGF1R (WOKVAC) T helper cells (Th) polyepitope plasmid based vaccine in patients with breast cancer at 3 escalating doses. II. To determine whether a WOKVAC Th polyepitope plasmid based vaccine elicits a persistent memory T cell response. III. To evaluate whether WOKVAC vaccination modulates T regulatory cells (Treg) and myeloid derived suppressor cells (MDSC). IV. To evaluate changes in mammographic density using clinically available images prior to baseline and post vaccination as an exploratory analysis. V. To determine a recommended phase 2 WOKVAC dose for further breast cancer prevention studies. 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with non-metastatic, node positive, HER2 negative breast cancer, confirmed by pathology report, who are in remission and defined as having no evidence of disease (NED); HER2 negative is defined as
- •0-1+ HER2 expression by immunohistochemistry (IHC) OR
- •Fluorescence in situ hybridization (FISH) negative OR
- •HER2 2+ and FISH negative
- •Patients must be at least 28 days post cytotoxic chemotherapy, radiotherapy, monoclonal antibody and/or other biologic therapy, prior to enrollment; patients on bisphosphonates, denosumab, and/or endocrine therapy and may continue throughout duration of study
- •Patients must be at least 28 days post systemic steroids prior to enrollment
- •Patients must have Eastern Cooperative Oncology Group (ECOG) performance status score of =\< 2
- •White blood cell (WBC) \>= 3000/mm\^3
- •Hemoglobin (Hgb) \>= 10 g/dl
- •Lymphocyte count \>= 800/mm\^3
Exclusion Criteria
- •Patients with any of the following cardiac conditions:
- •Symptomatic restrictive cardiomyopathy
- •Dilated cardiomyopathy
- •Unstable angina within 4 months prior to enrollment
- •New York Heart Association functional class III-IV heart failure on active treatment
- •Symptomatic pericardial effusion
- •Patients may not be receiving any other investigational agents
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to WOKVAC
- •Patients with any contraindication or known hypersensitivity to receiving sargramostatin (recombinant human granulocyte macrophage colony stimulating factor \[rhuGM-CSF\]) or other yeast based products
- •Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with this vaccine
Arms & Interventions
Treatment (WOKVAC with sargramostim)
Patients receive WOKVAC with sargramostim 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 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.
Intervention: Laboratory Biomarker Analysis
Treatment (WOKVAC with sargramostim)
Patients receive WOKVAC with sargramostim 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 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.
Intervention: pUMVC3-IGFBP2-HER2-IGF1R Plasmid DNA Vaccine
Treatment (WOKVAC with sargramostim)
Patients receive WOKVAC with sargramostim 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 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.
Intervention: Sargramostim
Outcomes
Primary Outcomes
Number of Adverse Events Per Common Terminology Criteria for Adverse Events Version 4.0
Time Frame: Up to 9 months
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.
Secondary Outcomes
- Assessment of IgG Antibodies(Up to 4 months)
- Assessment of T Helper Th1:Th2 Ratio(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(Up to 24 weeks)
- Level of Antigen Specific Central and Effector Memory Phenotypes (Persistent Memory T Cell Response)(Up to 6 months after the last vaccine)
- Modulation of Myeloid Derived Suppressor Cell Levels(Up to 24 weeks)
- Modulation of T Regulatory Cell Levels(Up to 24 weeks)