Alteration of the Immune Microenvironment in Basal Cell Carcinoma (BCC) Following Photodynamic Therapy (PDT)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Time to maximum expression of immune checkpoint molecules
研究概览
简要总结
The purpose of this study is to better understand the immune response to basal cell carcinoma (BCC) treated with Photodynamic Therapy (PDT) in order to develop new methods of treating BCC. Previous research suggests that PDT alters the immune response, possibly in a way that could promote better tumor clearance when combined with other treatments. Overall, participation in this study will help the study team better understand the anti-tumor immune response when BCC is treated with PDT.
详细描述
PDT is a technique that works by combining a photosensitizing topical agent and an intense light to kill tumor cells. PDT is not currently approved for the treatment of BCC by the Food and Drug Administration (FDA), although it is approved for that purpose in many European countries.
This is an internally (bilaterally) controlled trial that will enroll 24 participants with biopsy-proven BCC who are planning to undergo tumor removal via Mohs surgery. Within this cohort, one tumor will be PDT-treated and the other left as an untreated control. This study is also a cohort-controlled trial, because discarded tissue from fully de-identified Mohs participants will be analyzed after routine Mohs surgery, in order to establish the baseline variability in tumor-infiltrating immune cell parameters in non-PDT-treated participants.
The objectives of this study are:
To determine the time to maximum expression of immune checkpoint molecules in BCC tumors and peri-tumoral stroma after PDT, as compared to untreated tumors.
To determine the ratio of cytotoxic T cells to regulatory T cells in BCC tumors and peri-tumoral stroma after PDT, as compared to untreated tumors.
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
- •Must be an adult parcticpant (> 18 yrs) who is scheduled to undergo BCC surgery (via Mohs surgery, ED&C, or standard elliptical excision) within the Dermatologic Surgery unit of the Department of Dermatology, Cleveland Clinic.
- •Must have at least one BCC tumor eligible for surgical removal
- •Participants of any ethnic group are eligible for this trial.
- •Must provide informed consent to participate in the trial.
排除标准
- •Pregnant or breastfeeding
- •Currently being treated for other cancers with medical or radiation therapy
- •Known hypersensitivity to 5-aminolevulinic acid
- •History of a photosensitivity disease, e.g., porphyria cutanea tarda
研究组 & 干预措施
Photodynamic therapy (PDT)
Each participant will serve as their own control, receiving PDT for one tumor, no PDT for the second tumor (untreated control).
Visit 1:
- Informed consent
- Blood draw
- Lesion(s) Photographed
- (ALA) applied for4 hours
- PpIX measured in lesions (PpIX buildup monitored every 30 minutes over a 4 h period)
- PDT with blue light
Visit 2 (scheduled for within one of the following time intervals: 1-3 days, 4-7 days, or 8-14 days post-PDT):
- Blood draw
- Lesion(s) Photographed
- Mohs surgery
- After procedure, excess frozen BCC tissue will be saved for analysis
干预措施: ALA (Drug)
Photodynamic therapy (PDT)
Each participant will serve as their own control, receiving PDT for one tumor, no PDT for the second tumor (untreated control).
Visit 1:
- Informed consent
- Blood draw
- Lesion(s) Photographed
- (ALA) applied for4 hours
- PpIX measured in lesions (PpIX buildup monitored every 30 minutes over a 4 h period)
- PDT with blue light
Visit 2 (scheduled for within one of the following time intervals: 1-3 days, 4-7 days, or 8-14 days post-PDT):
- Blood draw
- Lesion(s) Photographed
- Mohs surgery
- After procedure, excess frozen BCC tissue will be saved for analysis
干预措施: PDT (Procedure)
结局指标
主要结局
Time to maximum expression of immune checkpoint molecules
时间窗: at visit 2 (1-14 days)
Time (days) to maximum expression of immune checkpoint molecules in BCC tumors and peri-tumoral stroma after PDT, as compared to untreated tumors. Data from frozen BCC specimens post-PDT by immunostaining the tumor specimens with antibodies against PD-L1, PD-1, CTLA-4 as well as the newer IC molecules TIGIT, TIM-3, and LAG-3
Altered expression of immune checkpoint molecules
时间窗: at visit 2 (1-14 days)
Altered expression of immune checkpoint molecules in BCC tumor specimens after PDT. Assessed by comparing IC molecule expression in PDT treated and untreated tumors with immunostaining in the tumor specimens with antibodies against PD-L1, PD-1, CTLA-4 as well as the newer IC molecules TIGIT, TIM-3, and LAG-3. (quantifying with immunofluorescence microscope)
Altered recruitment of different immune cell subtypes in BCC tumor specimens
时间窗: at visit 2 (1-14 days)
Determine the ratio of cytotoxic T cells to regulatory T cells in BCC tumors and peri-tumoral stroma after PDT, as compared to untreated tumors. Measured with specific antibodies against the following markers, to determine the qualitative time course of infiltration by each immune cell populations: Neutrophils (Gr1+ or MPO+); Macrophages(F4/80+); MDSCs (CD33, S100A9); cytotoxicT-cells(CD8+); regulatory T-cells(CD4+,FoxP3+,CD25+, CD127-); NK natural killer cells(CD56+CD16+).
次要结局
- Proportion of tumor-activated CD8+ T-cells after PDT(at visit 2 (1-14 days))
- Rate of protoporphyrin IX (PpIX) accumulation in tumors(Every 30 minutes up to 4 hours)
- Maximal PpIX levels in tumors(Every 30 minutes up to 4 hours)
- Change in the color of tumors(at visit 1 (pre PDT) and visit 2 (1-14 days))
- Change in the appearance of tumors(at visit 1 (pre PDT) and visit 2 (1-14 days))
- Change in the volume of tumors(at visit 1 (pre PDT) and visit 2 (1-14 days))
- Distant tumor (abscopal) effects after PDT(at visit 2 (1-14 days))
- To determine the relationship of PDT with the expression of immune- and cancer-associated RNA molecules(at visit 1 (pre PDT) and visit 2 (1-14 days))