Phase IIA Trial of 1% Topical Cidofovir for Treatment of High-Grade Perianal Squamous Intraepithelial Lesions in HIV-Infected Men and Women
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 33
- 试验地点
- 8
- 主要终点
- Proportion of Patients With Regression of Perianal High-grade Squamous Intraepithelial Lesions (HSIL)
研究概览
简要总结
RATIONALE: High-grade squamous intraepithelial lesions of the skin near the anus are caused by the human papillomavirus (HPV). Antiviral drugs,, such as cidofovir, act against viruses and may stop these lesions from becoming cancer.
PURPOSE: This phase II trial is studying the side effects and how well topical cidofovir works in treating HIV-infected patients with high-grade squamous intraepithelial lesions of the skin near the anus.
详细描述
OBJECTIVES:
Primary
- To evaluate the safety and tolerability of topical cidofovir in HIV-infected patients with perianal high-grade squamous intraepithelial lesions (HSIL).
- To estimate the regression rate of perianal HSIL in patients treated with this regimen.
Secondary
- To determine the human papilloma virus (HPV) DNA types and HPV strain variants present in perianal HSIL and normal perianal tissue.
- To determine if clinical regression of perianal HSIL is associated with clearance of HPV DNA.
- To identify the HPV DNA types present in the anus and cervix and compare them with the HPV DNA present in the perianus in order to determine if the HPV types associated with the perianal lesions are the same as those infecting the anus and cervix.
- To determine if there are abnormally methylated genes in perianal HSIL compared with normal perianal tissue and if these genes are the same or different from those that have been previously identified in anal and cervical dysplasia.
- To determine whether methylated genes are changed after treatment with cidofovir.
- To characterize differences in gene expression in perianal HSIL compared with normal perianal tissue.
- To examine changes in gene expression in perianal HSIL after exposure to cidofovir using RNA microarray analysis and confirm results with real-time polymerase chain reaction.
- To correlate pretreatment CD4 count, viral load, lesion size, methylation pattern, and/or HPV type and strain with the clinical efficacy of topical cidofovir.
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
Cidofovir
1.0% topical cidofovir cream
干预措施: cidofovir (Drug)
Cidofovir
1.0% topical cidofovir cream
干预措施: DNA methylation analysis (Genetic)
Cidofovir
1.0% topical cidofovir cream
干预措施: gene expression analysis (Genetic)
Cidofovir
1.0% topical cidofovir cream
干预措施: polymerase chain reaction (Genetic)
Cidofovir
1.0% topical cidofovir cream
干预措施: biopsy (Procedure)
Cidofovir
1.0% topical cidofovir cream
干预措施: histopathologic examination (Procedure)
结局指标
主要结局
Proportion of Patients With Regression of Perianal High-grade Squamous Intraepithelial Lesions (HSIL)
时间窗: 6 weeks after treatment discontinuation
Safety and Tolerability of Topical Cidofovir as Assessed by NCI CTCAE v3.0
时间窗: Every 2 weeks on study, 6 weeks after treatment discontinuation
Number of study patients who had a serious adverse event
次要结局
- Correlation of Clinical Regression of Perianal HSIL With Clearance of HPV DNA(6 weeks after treatment discontinuation)
- Identification of HPV-DNA Types Present in the Anus(Baseline)
- Human Papilloma Virus (HPV) DNA Type in Perianal HSIL and Normal Perianal Tissue(Baseline)
- Identification of Abnormally Methylated Genes in Perianal Dysplasia(Baseline, after cycle 1, and 6 weeks after treatment discontinuation)
- Distribution of Abnormally Methylated Genes Among HSIL, Low-grade Squamous Intraepithelial Lesions, and Normal Perianal Skin(Baseline, after cycle 1, and 6 weeks after treatment discontinuation)
- Changes in Gene Expression in Perianal HSIL After Exposure to Cidofovir as Assessed by RNA Microarray Analysis(Baseline, after cycle 1, and 6 weeks after treatment discontinuation)