Phase I/II Study of Combination Immunotherapy for the Generation of HER-2/Neu (HER2) Specific Cytotoxic T Cells (CTL) in Vivo
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 2
- 主要终点
- Immune Response Measured by IFN-gamma Secreting PBMC Precursor Frequency by ELIspot and HLA-A2 Major Histocompatibility Complex Tetramer Analysis
研究概览
简要总结
This phase I/II trial studies the side effects of vaccine therapy and to see how well it works in treating patients with stage IV major histocompatibility complex, class I, A2 antigen (HLA-A2) and human epidermal growth factor receptor 2 (HER2) positive breast or ovarian cancer who are receiving trastuzumab. Giving booster vaccines made from HER2 peptides may help increase HER2 specific immunity and immune memory cells.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the safety of administering a HER2 cytotoxic T-cell (CTL) peptide-based vaccine (HER-2/neu peptide vaccine) to stage IV breast and ovarian cancer patients receiving maintenance trastuzumab.
II. To quantify and characterize antigen specific T cell subsets specific to HER2 in peripheral blood mononuclear cell (PBMC) of patients after vaccination with a HER2 CTL peptide-based vaccine while receiving maintenance trastuzumab.
SECONDARY OBJECTIVES:
I. To evaluate overall survival (OS) in patients who complete a vaccination series with a HER2 CTL peptide-based vaccine while receiving maintenance trastuzumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Subjects must have either stage IV breast or ovarian cancer in remission or with stable disease on trastuzumab monotherapy
- •HER2 overexpression by immunohistocytochemistry (IHC) of 2+ or 3+, in the primary tumor or metastasis; if overexpression is 2+ by IHC, then patients must have HER2 gene amplification documented by fluorescence in situ hybridization (FISH)
- •Subjects must be HLA-A2 positive
- •Eligible subjects must have completed appropriate treatment for their primary disease and be off cytotoxic chemotherapy and any immunosuppressive agents such as systemic steroids for at least 30 days prior to enrollment; patients should continue trastuzumab monotherapy throughout the course of this protocol; concurrent hormonal and biphosphonate therapies are allowed
- •Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status score = 0 or 1
- •Male subjects must agree to contraceptive use during the study period (7 months) and non-menopausal female subjects must agree to contraception for the remainder of their childbearing years
- •Hematocrit >= 30 performed within 60 days of enrollment
- •Platelet count >= 100,000 performed within 60 days of enrollment
- •White blood cells (WBC) >= 3000/ul performed within 60 days of enrollment
- •Stable creatinine =< 2.0 mg/dL or creatinine clearance >= 60 ml/min performed within 60 days of enrollment
- •Serum bilirubin < 1.5 mg/dl performed within 60 days of enrollment
- •Serum glutamic-oxaloacetic transaminase (SGOT) < 2 x upper limit of normal (ULN) performed within 60 days of enrollment
- •Subjects must have recovered from major infections and/or surgical procedures and, in the opinion of the investigator, not have a significant active concurrent medical illness precluding protocol treatment or survival
- •Patients must have a baseline left ventricular ejection fraction (LVEF) measured by multi-gated acquisition scan (MUGA) equal to or greater than the lower limit of normal for the radiology facility and if there are two consecutive MUGAS performed while on trastuzumab from the same radiology facility, there cannot be a decrease in LVEF of > 15% from the original MUGA scan
排除标准
- •Subjects cannot be simultaneously enrolled on other treatment studies
- •Any contraindication to receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) based vaccine products
- •Cardiac disease, specifically restrictive cardiomyopathy, unstable angina within the last 6 months prior to enrollment, New York Heart Association functional class III-IV heart failure on active treatment with normalized LVEF on therapy, and symptomatic pericardial effusion
- •Active autoimmune disease
- •Subjects cannot have an active immunodeficiency disorder, e.g. human immunodeficiency virus (HIV)
结局指标
主要结局
Immune Response Measured by IFN-gamma Secreting PBMC Precursor Frequency by ELIspot and HLA-A2 Major Histocompatibility Complex Tetramer Analysis
时间窗: Up to 1.5 years (12 months following the last vaccination)
ELIspot: Increased immune response is defined as spots per well (SPW) greater than 2 standard deviations (SD) above baseline value, remained the same if the mean SPW was within 2 SD of the previous value, or decreased if the mean SPW was greater than 2 SD below the previous value. Two SD is equivalent to a P value of .05 in that there is a 95% probability that the values are statistically significant. T is reported as percentage of patients and their corresponding results. HLA-A2 Major Histocompatibility Complex Tetramer Analysis is evaluated using a non-radioactive assay for cell lysis. The HLA-A2 transfected human HER2/neu expressing breast cancer cell line, SKBR3-A2 T cells, expanded after stimulation with immunizing peptide, were added in an effector/target ratio of 40:1. Percent specific lysis was calculated as: (\[experimental release-spontaneous releases of cytotoxic T-lymphocyte cells and target cells\]/\[maximum release-spontaneous release of target cells\])X100.
Number of Adverse Events Graded Using National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0
时间窗: Up to 7 months (30 days following the last vaccination)
Descriptive statistics will be used to summarize changes from baseline. At the point the participant signs consent and before they start vaccine we record their existing baseline events (symptoms and diagnoses) and assign a grade to them (see below). Once a participant starts vaccine treatment adverse event AEs were recorded if they are new to the participant or if they increased in severity over their baseline. Grade refers to the severity of the AE. The CTCAE v3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
次要结局
- Overall Survival(Up to 5 years)
研究者
Mary (Nora) Disis
Professor, University of Washington
University of Washington