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
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Number of Adverse Events Per Common Terminology Criteria for Adverse Events Version 4.0
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Platelet count >= 75,000/mm^3
- •Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min
- •Total bilirubin =< 1.5 mg/dl
- •Aspartate aminotransferase (AST)/Serum glutamic oxaloacetic transaminase (SGOT) =< 2 times upper limit of normal (ULN)
- •Glycosylated hemoglobin measurement (HbA1c) < 5.7%
- •Patients must have recovered from major infections and/or surgical procedures, and in the opinion of the investigator, not have any significant active concurrent medical illnesses precluding protocol treatment
- •Patients who are having sex that can lead to pregnancy must agree to use adequate contraception (hormonal, barrier method of birth control, or abstinence) for the duration of study participation; should a woman become pregnant while participating in the study, she should inform her study doctor immediately and will not receive any more study treatment
- •Left ventricular ejection fraction (LVEF) results must be >= lower limit of normal (LLN) for institution performing based on results from the multi-gated acquisition (MUGA) or echocardiogram (ECHO) done at baseline
- •Willing to not undergo any elective surgical procedure with general anesthesia or conscious sedation through the 1 month post-vaccination visit
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •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
- •History of diabetes
- •Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
- •History of autoimmunity that has not been controlled with treatment in the last 12 months
研究组 & 干预措施
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: pUMVC3-IGFBP2-HER2-IGF1R Plasmid DNA Vaccine (Biological)
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.
干预措施: Sargramostim (Biological)
结局指标
主要结局
Number of Adverse Events Per Common Terminology Criteria for Adverse Events Version 4.0
时间窗: 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.
次要结局
- 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)