A Phase I, Open Label Study Employing the Topical Immunomodulator Diphencyprone to Treat Cutaneous Neurofibromas Associated With NF1
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Symptom standardized assessment scale
研究概览
简要总结
Neurofibromatosis type 1 (NF1) is the most common genetic tumor predisposition syndrome, affecting up to 1 in 2500 individuals. Cutaneous neurofibromas are benign with self-limited growth; however, tumor burden may be excessive, tumors do not regress, and they can be disfiguring, painful, and itchy. Currently, the only treatment is surgery or laser ablation; however, outcomes are limited by the number of tumors that can be simultaneously removed, operating room availability, and painful recovery, with significant risk of regrowth. There is a strong need for noninvasive topical treatments for cutaneous neurofibromas. Diphencyprone (DPCP) is a "hapten" medication, a small molecule that activates the immune system when applied topically, which has been investigated as a cutaneous immunotherapy for other skin conditions.
This is an open label Phase I study looking at safety and tolerability of this treatment as a primary endpoint, and tumor treatment as a secondary endpoint. Approximately 30 subjects will be enrolled at a single center within the US. Subjects with a clinical diagnosis of NF1 who have measurable disease and at least 4 cutaneous neurofibromas, will have DPCP applied topically to their neurofibromas once weekly for 10 weeks.
详细描述
Each subject after consent will undergo a biopsy of one cutaneous neurofibroma prior to treatment. The participant will then undergo a sensitization treatment to "normal" skin as well as one neurofibroma to activate the immune system against the trial drug. 14 days after sensitization, patients will begin the first of 10 weekly treatment doses to a minimum of 3, up to 20 cutaneous neurofibromas. The participant may require up to 2 additional sensitization exposures. When the investigator has determined that sensitization has occurred, each subject will have a skin biopsy of one treated neurofibroma 3 days after initial treatment on Day 17 in order to investigate cellular and molecular effects of the treatment. The remainder of treatments will be applied once weekly on days 21, 28, 35, 42, 49, 56, 63, 70, and 77. The followup visit will occur on Day 107. Tumors will be photographed at screening and at each treatment visit, and in addition, whole body photography will be performed on Day 0 and Day 107 to assess for off-target effects on cutaneous neurofibromas that were not directly treated. On Day 107, a third cutaneous neurofibroma will be biopsied for molecular and immunohistopathological outcomes.
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 —（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
DPCP
0.4% ointment
干预措施: DPCP (Drug)
结局指标
主要结局
Symptom standardized assessment scale
时间窗: at Day 77 or 107
Tolerability of DPCP will be measured by the subjective response of patients who experience symptoms directly related to the therapy. Specifically, the subject will report their own symptoms of local tolerability based on a standardized assessment scale. The subject will assess pain, stinging, burning, and pruritus using a 4-point scale (0 none, 1 mild, 2 moderate, 3 severe) for each treated target lesion. Each of the four domains will be graded on the 4-point scale, each domain range from 0-16, with higher score indicating more severe symptoms. There is no overall score.
Proportion of subjects with a grade 3 adverse event
时间窗: at Day 77 or 107
Safety of DPCP will be measured as the proportion of subjects with a grade 3 on the Common Terminology Criteria for Adverse Events (CTCAE) criteria. Specifically, the safety of DPCP will be assessed as per CTCAE for eczema, version 5.0.
次要结局
未报告次要终点
研究者
Nicholas Gulati
Assistant Professor
Icahn School of Medicine at Mount Sinai