Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma and Other Solid Tumors
Phase I/IIa AdCD40L Immunogene Therapy for Patients With Advanced Malignant Disease.
研究概览
详细说明
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.
研究类型
注册 (实际的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
-
-
-
Uppsala、瑞典、75185
- Uppsala University Hospital
-
-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Histologically proven diagnosis of malignant solid cancer, ECOG 0-2.
- Disease progression on established treatments or patients not eligible to standard options.
- Signed informed consent must be obtained.
Exclusion Criteria:
- 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.
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：AdCD40L
Treatments once a week with 2.5x10e11 VP AdCD40L, maximum 4 treatments (total dose 1x10e12 VP).
If no effect in less than 2 out of 6 melanoma patients, the following 9 melanoma patients and 6 patients with other solid tumors will receive preconditioning therapy 1-2 days prior to first and last treatment with 300mg/m2 cyclophosphamid.
The next 9 melanoma patients will receive one local radiotherapy.
|
Adenoviral serotype 5 vector, E1/E3 deleted.
Human CD40L gene insert driven by RSV promoter.
Vector diluted in infusion solution, 500uL solution containing 2.5x10e11 VP is intratumorally injected/treatment.
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
All cause adverse events
大体时间：during 10 weeks
|
Adverse events will be documented such as inflammation, fever, pain, changes in blood pressure, pulse etc.
|
during 10 weeks
|
|
Immune reactions to adenovirus and spreading of vector
大体时间：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).
|
during 10 weeks
|
次要结果测量
结果测量 |
大体时间 |
|---|---|
|
Tumor burden as measured by PET/CT and whole body MR
大体时间：At enrollment, week 5 and week 9
|
At enrollment, week 5 and week 9
|
合作者和调查者
调查人员
- 学习椅：Thomas H Tötterman, MD, PhD、Uppsala University
- 首席研究员：Gustav Ullenhag, MD, PhD、Uppsala University Hospital
- 研究主任：Angelica SI Loskog, PhD、Uppsala University
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.