Phase I/IIa AdCD40L Immunogene Therapy for Patients With Advanced Malignant Disease.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- All cause adverse events
研究概览
简要总结
In this phase I/II trial, immunostimulatory gene therapy (AdCD40L) will be investigated. In Part 1 patients with melanoma will receive AdCD40L as mono therapy. In Part 2A, patients with melanoma and patients with other solid tumors will receive AdCD40L in combination with low dose cyclophosphamide. In Part 2B, patients with melanoma will receive AdCD40L in combination with one local radiotherapy and cyclophosphamide.
详细描述
In this phase I/II trial, immunostimulatory gene therapy (AdCD40L) will be investigated. In Part 1 patients with melanoma (n=6) will receive AdCD40L as mono therapy. In Part 2A, patients with melanoma (n=9) and patients with other solid tumors (n=6) will receive AdCD40L in combination with low dose cyclophosphamide. In Part 2B, patients with melanoma will receive AdCD40L in combination with one local radiotherapy and cyclophosphamide. AdCD40L is given by weekly injections of 2.5x10e11 VP, 4x; total dose 1x10e12 VP. A maximum of 30 patients will be included in this trial.
AdCD40L is an adenoviral nonreplicating vector carrying the human CD40L gene. AdCD40L infects tumor cells upon intratumoral injection and deliver the CD40L gene into the cells whereupon the virus is destroyed. CD40L is then expressed as a membrane-bound protein and interacts with the CD40 receptor expressed by for example dendritic cells (DCs) in the tumor area. DCs mature upon CD40/CD40L interactions and activates tumor-specific T cell responses.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven diagnosis of malignant solid cancer, ECOG 0-
- •Disease progression on established treatments or patients not eligible to standard options.
- •Signed informed consent must be obtained.
排除标准
- •Pregnancy.
- •Life expectancy less than 3 months.
- •Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures.
- •Patients with severe systemic autoimmune disease.
- •Patients that do not consent to that tissue and blood samples are stored in a biobank.
结局指标
主要结局
All cause adverse events
时间窗: during 10 weeks
Adverse events will be documented such as inflammation, fever, pain, changes in blood pressure, pulse etc.
Immune reactions to adenovirus and spreading of vector
时间窗: during 10 weeks
Immune reactions to adenovirus will be measured by evaluating the increase of anti-adenoviral antibodies in the patients at different time points using an ELISA. Spreading of vector will be evaluated by real time PCR to detect adenovirus vector copies in blood (plasma and erythrocyte fraction).
次要结局
- Tumor burden as measured by PET/CT and whole body MR(At enrollment, week 5 and week 9)