A Phase 0 Trial of Hydroxychloroquine, an Inhibitor of Autophagy, in Patients With Stage III or IV Resectable Melanoma
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Modulation of markers of autophagy by hydroxychloroquine (HCQ), as measured by p62, Beclin1, LC3, and GRp170 expression
研究概览
简要总结
RATIONALE: Studying samples of blood, tumor tissue, and skin in the laboratory from patients with melanoma receiving hydroxychloroquine may help doctors understand the effect of hydroxychloroquine on biomarkers.
PURPOSE: This early phase I trial is studying hydroxychloroquine in patients with stage III or stage IV melanoma that can be removed by surgery.
详细描述
OBJECTIVES:
Primary
- To characterize the effects of hydroxychloroquine (HCQ) on the modulation of markers of autophagy, as measured by p62, Beclin1, LC3, and GRp170 expression, in pre- and post-treatment tumor biopsy samples, skin samples, and peripheral blood mononuclear cell samples from patients with stage III or IV melanoma undergoing palliative or curative surgery.
Secondary
- To determine whether the steady-state plasma concentration of HCQ correlates with observed trends in induced markers of autophagy.
- To determine the potential mechanisms of antitumor effect of HCQ, as measured by a reduction in tumor cell proliferation (Ki-67 and mitotic rate) or an increase in apoptosis (activated caspase-3 and TUNEL assays) in melanoma specimens.
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 120 Years（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
研究组 & 干预措施
Hydroxychloroquine
Patients must have tumor accessible for pre-treatment biopsy (see 5.1.2). Patients will be enrolled on the trial, undergo biopsy of their tumors if no banked tumor is available, and then begin an oral dose of HCQ at the dose of 200 mg twice daily. At the end of two weeks the patients will undergo resection of their tumors. HCQ will be given to the patients up to the day of the operation but not resumed postoperatively.
干预措施: hydroxychloroquine (Drug)
结局指标
主要结局
Modulation of markers of autophagy by hydroxychloroquine (HCQ), as measured by p62, Beclin1, LC3, and GRp170 expression
时间窗: 1 year
次要结局
- Correlation of steady-state plasma concentration of HCQ with observed trends in induced markers of autophagy(1 year)
- Potential mechanisms of antitumor effect of HCQ, as measured by a reduction in tumor cell proliferation or an increase in apoptosis(1 year)