An Open-label, Neoadjuvant Phase 2 Study Comparing the Effects of AR Inhibition With and Without SRC or MEK Inhibition on the Development of EMT in Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- N-cadherin and vimentin expression
研究概览
简要总结
Prostate cancer is the most common cancer in men and the second leading cause of cancer death in men. The purpose of this research study is to compare prostate cancers treated with hormone therapy versus prostate cancers treated with hormone therapy plus drugs that directly target cancer cells.
详细描述
Most prostate cancers respond to hormone therapy, also known as chemical castration. Unfortunately, castration resistance may occur in certain prostate cancers. Castration resistance or hormone refractory prostate cancer means that the cancer continues to progress as seen by progressively rising PSA and/or or an increase in tumor mass on bone scan, X-ray, CT scan or MRI despite previous hormonal therapy. The researchers are interested in understanding mechanisms of castration resistance in prostate cancer by analyzing prostate tissue before radical prostatectomy (from prostate biopsy tissue) and after radical prostatectomy (whole prostate specimen). They will look at the "molecular signature" of prostate cancer cells after hormone therapy to identify the key steps that the cancer cells undergo to become resistant to hormone therapy. In addition, the researchers will use other medications in addition to hormone therapy in order to block some of the key biochemical steps that are thought to mediate treatment resistance. This research will provide crucial information for the development of therapies that can improve the clinical outcome of patients with advanced prostate cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
AR inhibition only
AR inhibition only Group 1: degarelix + enzalutamide
Endocrine therapy with degarelix and enzalutamide will continue for a minimum of 6 weeks and a maximum of 8 weeks in all groups prior to the planned prostatectomy.
干预措施: degarelix (Drug)
AR inhibition only
AR inhibition only Group 1: degarelix + enzalutamide
Endocrine therapy with degarelix and enzalutamide will continue for a minimum of 6 weeks and a maximum of 8 weeks in all groups prior to the planned prostatectomy.
干预措施: enzalutamide (Drug)
AR inhibition plus MEK inhibition
AR inhibition plus MEK inhibition Group 2: trametinib + degarelix + enzalutamide
In Group 2, treatment with trametinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, trametinib will be administered for no less than two weeks and no more than four weeks.
干预措施: degarelix (Drug)
AR inhibition plus MEK inhibition
AR inhibition plus MEK inhibition Group 2: trametinib + degarelix + enzalutamide
In Group 2, treatment with trametinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, trametinib will be administered for no less than two weeks and no more than four weeks.
干预措施: enzalutamide (Drug)
AR inhibition plus MEK inhibition
AR inhibition plus MEK inhibition Group 2: trametinib + degarelix + enzalutamide
In Group 2, treatment with trametinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, trametinib will be administered for no less than two weeks and no more than four weeks.
干预措施: trametinib (Drug)
AR inhibition plus SRC inhibition
AR inhibition plus SRC inhibition Group 3: dasatinib + degarelix + enzalutamide
In Group 3, treatment with dasatinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, dasatinib will be administered for no less than two weeks and no more than four weeks.
干预措施: degarelix (Drug)
AR inhibition plus SRC inhibition
AR inhibition plus SRC inhibition Group 3: dasatinib + degarelix + enzalutamide
In Group 3, treatment with dasatinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, dasatinib will be administered for no less than two weeks and no more than four weeks.
干预措施: enzalutamide (Drug)
AR inhibition plus SRC inhibition
AR inhibition plus SRC inhibition Group 3: dasatinib + degarelix + enzalutamide
In Group 3, treatment with dasatinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, dasatinib will be administered for no less than two weeks and no more than four weeks.
干预措施: dasatinib (Drug)
结局指标
主要结局
N-cadherin and vimentin expression
时间窗: Prostatectomy will occur during the 2 week "window" between 6 and 8 weeks after enrollment
The primary outcome of N-cadherin and vimentin expression will be measured in post-treatment RP specimens. Comparisons amongst the various treatment groups (post-treatment inter-group) will be performed after all data have been collected.
次要结局
未报告次要终点