A Phase I Study of an Adenoviral Transduced Autologous Dendritic Cell Vaccine Expressing Human HER2/Neu ECTM in Adults With Tumors With 1-3+ HER2/Neu Expression
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 2
- 主要终点
- Number of Participants With Cardiac Toxicity
研究概览
简要总结
Background:
- Human epidermal growth factor receptor 2 (HER2, also known as c-erbB2 or neu)/neu (HER2) is a tumor protein that appears in almost a third of breast cancers and in several other types of cancers such as colon, prostate and non-small cell lung. Tumors that overexpress HER2 can be associated with a more aggressive cancer, higher recurrence rates, and reduced survival rates. Researchers are testing a therapeutic cancer vaccine designed to stimulate the immune system to recognize HER2. The vaccine, called adenoviral transduced autologous human epidermal growth factor receptor (AdHER)/neu dendritic cell vaccine, is custom-made using an individual's own immune cells. These cells will be collected and used to produce the vaccine.
Objectives:
- To test the safety and effectiveness of AdHER2 vaccination.
Eligibility:
- Individuals at least 18 years of age who have HER2-expressing tumors.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies will also be performed.
- Participants will have an apheresis procedure to collect immune cells to create the vaccine.
- Participants will receive five doses of the vaccine at study Weeks 0, 4, 8, 16 and 24.
- Participants will be monitored with physical exams, frequent blood tests and imaging studies.
详细描述
Background:
- Human epidermal growth factor receptor 2 (HER2, also known as c-erbB2 or neu) is a proto-oncogene that encodes a 185-kd transmembrane tyrosine kinase receptor that participates in receptor-receptor interactions that regulate cell growth, differentiation and proliferation. Its over-expression contributes to neoplastic transformation.
- HER2 is over-expressed in up to 25-30% of node-positive or node-negative primary breast cancers and is associated with clinically aggressive breast cancer, a high recurrence rate and reduced survival.
- Trastuzumab (Herceptin (Registered trademark)) is a recombinant humanized mouse monoclonal antibody (MAb) that binds to the extracellular (EC) domain of the HER2 receptor. Its clinical efficacy is limited to patients with 3+ HER2 tumor expression documented by immunohistochemistry (IHC) or a Vysis fluorescent in situ hybridization (FISH) ratio of greater than 2.2. IHC is a subjective measurement of HER2/neu protein while FISH is an objective measurement of amplification of the HER2 oncogene.
- Although the use of trastuzumab has been associated with improved clinical outcomes, a significant number of patients are unresponsive to therapy and most eventually experience clinical progression. At present no vaccine is available that induces patients to make their own anti-HER2 antibodies.
- We propose to investigate the use of an adenoviral vector (Ad5f35) expressing human HER2ECTM (Ad5f35HER2ECTM- AdHER2) to transduce autologous dendritic cells for therapeutic vaccination in patients with HER2 expressing solid tumors.
Objectives:
-To determine the safety and toxicity of autologous AdHER2 dendritic cell vaccination.
Specifically, to determine if the fraction of patients with cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a decrease in left ventricular ejection fraction (LVEF) >=10 percentage points, to a value LVEF to less than or equal to 53% (normal reference value for two-dimensional (2-D) echocardiography), is sufficiently low to warrant further development in subsequent trials.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 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
- 未提供
排除标准
- 未提供
结局指标
主要结局
Number of Participants With Cardiac Toxicity
时间窗: Baseline through receipt of last dose of vaccine, up to 24 weeks
Cardiac toxicity defined as cardiac dysfunction due to damage to the heart muscles or valves. Cardiac toxicity was assessed by serial echocardiography to determine left ventricular ejection fraction (LVEF) at baseline and following receipt of the last dose of vaccine. Cardiac toxicity is at least a 10% decline from the baseline in cardiac function. Normal LVEF is \>-53%. Below 53% is a cardiac dysfunction.
Number of Participants Who Develop at Least a 4-fold or 2.5- Fold Increase in Anti-Human Epidermal Growth Factor Receptor (HER2)/Neu Antibody Dilution Titers
时间窗: Baseline through last dose of vaccine, up to 24 weeks
Vaccine immunogenicity was determined by the number of participants who develop at least a 4-fold increase in antibody dilution titers over baseline at the time points measured. The antibody response following the vaccination was assessed using peptide-array and reported as fold increase compared to the baseline values using the cut-off of 4 fold per study definition of the vaccine immunogenicity and also of 2.5 fold to aid the interpretation of the result.
次要结局
- Number of Participants Who Experienced Tumor Shrinkage or Stabilization That is Sufficient by Modified Immune Response Related Criteria (irRC) to be Considered Stable Disease (SD), a Partial Response (PR) or Better (Complete Response (CR)(At 8, 16, 24, 36, 48, 76, 100, and 124 weeks after initial vaccination)
研究者
Hoyoung M. Maeng, M.D.
Principal Investigator
National Cancer Institute (NCI)