Phase I Trial of Adenovirus- Mediated IL-12 Gene Transduction in Patients With Radiorecurrent Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 主要终点
- maximum cytokine gene therapy level
研究概览
简要总结
The purpose of this research study is to test a new treatment for prostate cancer. We have been exploring the use of cytokine (immune stimulating) gene therapy by directly injecting a virus which produces a cytokine called interleukin-12 (IL-12) into the prostate gland to control tumor growth. We propose to explore the use of adenovirus-mediated human interleukin-12 (Ad.hIL-12) in patients with recurrent non-metastatic prostate cancer following radiation therapy in a Phase I trial. Participants will be placed in rising dose groups with the primary endpoint of learning the maximum dose that can safely be given by injection directly into the prostate gland. Toxicity will be determined through physical examination, laboratory values, and blood levels of cytokines. Evidence of an immune response against prostate proteins will also be monitored. If the treatment works, the cancer will shrink or not grow. This will be monitored by prostate specific antigen (PSA) levels in the blood. However, we do not know if this treatment will be effective. If the PSA continues to rise after treatment, participants will be taken off study and offered other treatment. There is no compensation for participation in this research study. There will be no charge for the treatment with gene therapy or the monitoring associated with this research study. Monitoring will occur in a specially designated clinical research center.
详细描述
Patients with radiorecurrent prostate cancer have few viable treatment options, both in terms of efficacy and morbidity. Local therapies fail even in highly selected patients due to locally advanced disease, microscopic metastases, and a worsening of the biology of cancer cells. Furthermore, attempts at salvage local treatments have the complications of incontinence, impotence and in some cases unremitting penile pain. Pre-clinical studies in a mouse model of prostate cancer have noted the potential benefit of adenovirus-mediated gene therapy to deliver IL-12 in this clinical scenario. This treatment was able to significantly growth suppress the injected tumor to prolong survival and reduce the number of pre-established metastases. The mechanisms underlying this activity involved both innate immunity (neutrophils and natural killer [NK] cells) and acquired immunity ( T cells) and enhanced expression of Fas to further sensitize Fas/Fas ligand (FasL) killing.
This is a Phase I study. Therefore, the primary objective is finding the Maximum Tolerated Dose. Within this realm will be monitoring of pro-inflammatory cytokines. Secondary aspects will involve correlating important mechanisms identified in the pre-clinical model: induction of T cells.
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
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •A local recurrence of prostate cancer (in or next to gland) following treatment by radiation therapy (either external beam or seed implantation)
- •Rising PSA (Prostate Specific Antigen) on at least three occasions separated by two weeks
- •Ultrasound guided biopsy to diagnose recurrent disease within the prostate
- •No evidence of prostate cancer that has spread on bone scan or Computed Tomography (CT) scan
- •No hormone therapy at time of enrollment to the research study
排除标准
- •Radical prostatectomy for treatment of prostate cancer
- •Detectable spread of prostate cancer on bone or CT scan
- •Immunosuppressive medication within two months of the study
- •Acute infection (any bacterial, viral, fungal infection requiring specific therapy)
- •HIV disease
- •Other significant medical or psychiatric conditions which pose high risk for an investigational study
结局指标
主要结局
maximum cytokine gene therapy level
时间窗: after 56 weeks, every 6 months up to 15 years
To study in a Phase I clinical trial the safety of intraprostatic injection of a replication incompetent adenovirus expressing hIL-12 in patients with radiorecurrent prostate cancer
次要结局
- serum pro-inflammatory cytokines levels(up to 15 years)
- To assess T cell responses pre and post-IL-12 treatment against prostate antigens(Day 28 post vector injection)
- To assess changes in PSA levels as a surrogate marker for prostate cancer following Ad.hIL-12 gene therapy(8 weeks after vector injection)
研究者
Simon Hall
MD
Icahn School of Medicine at Mount Sinai