Vaccine Therapy in Preventing Cancer Recurrence in Patients With Non-Metastatic, Node Positive, HER2 Negative Breast Cancer That is in Remission (WOKVAC)
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|ClinicalTrials.gov Identifier: NCT02780401|
Recruitment Status : Recruiting
First Posted : May 23, 2016
Last Update Posted : January 2, 2020
|Condition or disease||Intervention/treatment||Phase|
|HER2/Neu Negative No Evidence of Disease One or More Positive Axillary Nodes Stage IB Breast Cancer Stage II Breast Cancer Stage IIA Breast Cancer Stage IIB Breast Cancer Stage III Breast Cancer Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer||Other: Laboratory Biomarker Analysis Biological: pUMVC3-IGFBP2-HER2-IGF1R Plasmid DNA Vaccine Biological: Sargramostim||Phase 1|
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||September 2, 2016|
|Estimated Primary Completion Date :||December 30, 2020|
|Estimated Study Completion Date :||December 30, 2020|
Experimental: 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.
Other: Laboratory Biomarker Analysis
Biological: pUMVC3-IGFBP2-HER2-IGF1R Plasmid DNA Vaccine
- Incidence of toxicity assessed by adverse events per Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ]Type and grade of toxicities noted during the immunization regimen will be summarized. Duration of toxicities will also be summarized using descriptive statistics such as mean and standard deviation. The frequency and severity of adverse events will be summarized with a proportion and a 95% confidence interval.
- Assessment of IgG antibodies [ Time Frame: Up to 4 months ]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.
- Assessment of T helper Th1:Th2 ratio [ Time Frame: Up to 4 months ]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 if the ratio of magnitude of Th1 (IFN-gamma)/Th2 (IL-10) is >1.
- Assessment of the immunogenicity of WOKVAC by generation of IGFBP-2, HER2, and IGF-1R specific type 1 (Th1) T- cells [ Time Frame: Up to 4 months ]Immune responses will be measured by IFN-g enzyme-linked immunosorbent spot assay and summarized with mean and standard deviation. Each patient will be given a value at each immune evaluation that is the sum of the median response to HER2, IGFBP-2 or IGF1R, and a composite median would be calculated for each WOKVAC dose level. Patients will be considered to have generated antigen specific (IGFBP-2, HER2, and IGF-1R) Th1 T-cells if they have a ≥1:20,000 composite mean IFN-gamma (IFN-g) precursor frequency by IFN-g enzyme-linked immunosorbent spot assay or greater than 2 fold increase over basel
- Level of antigen specific central and effector memory phenotypes (Persistent memory T cell response) [ Time Frame: Up to 6 months after the last vaccine ]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.
- Modulation of myeloid derived suppressor cell levels [ Time Frame: Up to 6 months after the last vaccine ]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.
- Modulation of T regulatory cell levels [ Time Frame: Up to 6 months after the last vaccine ]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.
- Change in mammographic density assessed using clinically available images and the automated Cumulus software program [ Time Frame: Up to 6 months after the last vaccine ]Summarized with mean and standard deviation or median and range at pre- and post-vaccination in tabular and graphical formats, along with the change from pre- to post-vaccination in a similar manner by dose level.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02780401
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Mary L. Disis 206-616-1823 email@example.com|
|Principal Investigator: Mary L. Disis|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics||Recruiting|
|Madison, Wisconsin, United States, 53792|
|Contact: Kari B. Wisinski 608-262-2876 firstname.lastname@example.org|
|Principal Investigator: Kari Wisinksi|
|Principal Investigator:||Kari Wisinski||University of Wisconsin, Madison|