Vitamin D Effects on Immune Microenvironment of Nonmelanoma Skin Cancer After Photodynamic Therapy (PDT)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Expression of immune checkpoint molecules
研究概览
简要总结
This research study is for people who have been diagnosed with a nonmelanoma skin cancer (either basal cell carcinoma or squamous cell carcinoma) and are planning to receive either Mohs surgery or ED&C (electrodessication & curettage) as part of clinical care. The purpose of this study is to understand how photodynamic therapy (PDT) with or without Vitamin D can promote an immune response to skin cancer.
For this study, participants will be randomized (randomly assigned) and asked to take Vitamin D or placebo for 6 days and come to the clinic for a single PDT treatment 1-14 days prior to their surgery. At this visit, photographs of participant's skin cancer will be taken, and participants will undergo PDT treatment. The study team will also take photos on the day of Mohs surgery or ED&C. There will be up to two blood draws for research.
If participants do not want to come in for a PDT treatment prior to their Mohs surgery or ED&C, they will have the option to participate by only allowing the study team to collect data about their skin cancer and their tissue from Mohs surgery or ED&C.
详细描述
This research study explores the effect of photodynamic therapy (PDT) on nonmelanoma skin cancers (NMSC). NMSC are made up of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). PDT is a treatment for NMSC that may be used instead of surgery. PDT uses light and a special chemical reaction to kill cancer cells on the skin's surface. First, an agent called aminolevulinate (ALA) is put on the skin of the tumor. Then, a bright blue light is shined on the skin, which causes a chemical reaction to occur. This chemical reaction helps to damage and kill cancer cells.
NMSCs are common and can usually be cured with surgery. However, surgery can leave scars or result in disfigurement. This can be especially difficult for people who have tumors on their face or other visible or sensitive parts of the body. As an alternative to surgery, photodynamic therapy (PDT) is approved in Europe to treat BCC and SCC. However, because PDT does not work as well on thicker tumors, the U.S. FDA has not yet approved it for use on NMSC in this country. Investigators want to better understand how PDT damages and kills tumor cells, so that knowledge can be used to make the treatment more effective.
Vitamin D (VitD) is both a nutrient and a steroid-like hormone. Over 10+ years of research in investigators' laboratory has shown that VitD works well with PDT to treat NMSC. When participants receive a high dose of VitD before PDT, the treatment is able to clear the tumor more effectively. This has been shown in studies with mice that had early skin cancer, as well as mice with thick skin cancer. It has also been shown to be effective in participants with BCC. One reason that VitD may help is because it increases the amount of photosensitizing agent that can accumulate within the tumor, which helps to effectively kill cancer cells with PDT when light is applied. However, VitD has another important effect, which is that it helps to attract immune cells into the tumor. This effect has been seen in mouse models of SCC. The primary purpose of this study is to further investigate this immune mechanism in humans.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
盲法说明
Masking only applies to Arms 2 and 3, not Arm 1.
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 participant (> 18 yrs) who is scheduled to undergo Mohs surgery or ED&C within the Dermatologic Surgery unit of the Department of Dermatology, Cleveland Clinic.
- •Must have at least one BCC or SCC tumor eligible for removal by Mohs surgery.
- •The original tumor size prior to biopsy must be >1.0 cm (in the longest diameter).
- •Participants of any ethnic group are eligible for this trial.
- •Must provide informed consent to participate in the trial.
- •Participant must live in Ohio (Groups 2 & 3), because Research Pharmacy cannot ship the study drugs outside of the state.
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
Arm 3: Placebo + PDT prior to Mohs surgery or ED&C
Participants in Arms 2 and 3 will be randomized to receive either VitD or placebo prior to PDT and Mohs surgery or ED&C visit.
干预措施: Photodynamic therapy (PDT) (Other)
Arm 3: Placebo + PDT prior to Mohs surgery or ED&C
Participants in Arms 2 and 3 will be randomized to receive either VitD or placebo prior to PDT and Mohs surgery or ED&C visit.
干预措施: Mohs surgery or electrodessication & curettage (ED&C) (standard of care) (Procedure)
Arm 2: VitD + PDT prior to Mohs surgery or ED&C
Participants in Arms 2 and 3 will be randomized to receive either VitD or placebo prior to PDT and Mohs surgery or ED&C visit.
干预措施: Vitamin D (VitD) (Dietary Supplement)
Arm 3: Placebo + PDT prior to Mohs surgery or ED&C
Participants in Arms 2 and 3 will be randomized to receive either VitD or placebo prior to PDT and Mohs surgery or ED&C visit.
干预措施: Placebo (Other)
Arm 2: VitD + PDT prior to Mohs surgery or ED&C
Participants in Arms 2 and 3 will be randomized to receive either VitD or placebo prior to PDT and Mohs surgery or ED&C visit.
干预措施: Photodynamic therapy (PDT) (Other)
Arm 1: Participants donate discarded tissue for research (No VitD/Placebo + no PDT)
Participants in Arm 1 will donate discarded tissue from their scheduled standard of care Mohs surgery or ED&C. They will not be randomized to receive VitD or placebo and will not have PDT.
干预措施: Mohs surgery or electrodessication & curettage (ED&C) (standard of care) (Procedure)
Arm 2: VitD + PDT prior to Mohs surgery or ED&C
Participants in Arms 2 and 3 will be randomized to receive either VitD or placebo prior to PDT and Mohs surgery or ED&C visit.
干预措施: Mohs surgery or electrodessication & curettage (ED&C) (standard of care) (Procedure)
结局指标
主要结局
Expression of immune checkpoint molecules
时间窗: At time of Mohs surgery or ED&C, up to Day 20
Expression of immune checkpoint molecules will be compared in tumors and peri-tumoral stroma after photodynamic therapy (PDT) versus tumors without PDT and is defined as changes in the expression of PD-1, PD-L1, and TIM3, among other checkpoint inhibitors. This will be measured using the scRNA-seq data obtained from tumor tissues via Parse Biosciences scRNA-seq analysis.
次要结局
- Ratio of cytotoxic T cells to regulatory T cells(At time of Mohs surgery or ED&C, up to Day 20)
- Ratio of M1 macrophages to M2 macrophages(At time of Mohs surgery or ED&C, up to Day 20)
- Proportion of tumor-activated CD8+ T-cells in circulating T-cells(At time of Mohs surgery or ED&C, up to Day 20)