Basal Cell Carcinoma, Nonmelanoma Skin Cancer, Squamous Cell Carcinoma
Conditions
Keywords
Mohs surgery, Electrodessication & curettage, ED&C, Photodynamic therapy, PDT, Vitamin D
Brief summary
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.
Detailed description
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.
Interventions
DIETARY_SUPPLEMENTVitamin D (VitD)
Participants will orally take 10,000 international units daily of VitD for the 6 days prior to their scheduled PDT visit. Participants in Arms 2 and 3 will be blinded to whether they are receiving VitD or placebo.
OTHERPlacebo
Participants will orally take a placebo (gelatin) capsule for the 6 days prior to their scheduled PDT visit. Participants in Arms 2 and 3 will be blinded to whether they are receiving VitD or placebo.
PDT involves a topical photosensitizing agent called aminolevulinate (ALA) being applied to the tumor surface. ALA is then activated by shining a blue light on the skin, causing a photodynamic reaction to occur. Participants will receive PDT 1-14 days prior to their scheduled Mohs surgery or ED\&C visit.
PROCEDUREMohs surgery or electrodessication & curettage (ED&C) (standard of care)
Participants are eligible for this study by already planning to undergo Mohs surgery or ED\&C, which will be conducted per standard of care. For Arms 2 and 3, participants will undergo Mohs surgery or ED\&C 1-14 days after their PDT visit. For Arm 1, participants will undergo Mohs surgery or ED\&C at their scheduled time. All participants donate their discarded tissue from the Mohs surgery for research.
Sponsors
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Masking description
Masking only applies to Arms 2 and 3, not Arm 1.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Expression of immune checkpoint molecules | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of cytotoxic T cells to regulatory T cells | At time of Mohs surgery or ED&C, up to Day 20 | Ratio of cytotoxic T cells to regulatory T cells will be compared in tumors and peri-tumoral stroma after photodynamic therapy (PDT) versus tumors without PDT. This is measured using scRNA-seq data (Parse Bioscienes scRNA-sequencing kit). |
| Ratio of M1 macrophages to M2 macrophages | At time of Mohs surgery or ED&C, up to Day 20 | Ratio of M1 macrophages to M2 macrophages will be compared in tumors and peri-tumoral stroma after photodynamic therapy (PDT) versus tumors without PDT. This is measured using scRNA-seq data (Parse Bioscienes scRNA-sequencing kit). |
| Proportion of tumor-activated CD8+ T-cells in circulating T-cells | At time of Mohs surgery or ED&C, up to Day 20 | Proportion of tumor-activated CD8+ T-cells in circulating T-cells will be compared in tumors and peri-tumoral stroma after photodynamic therapy (PDT) versus tumors without PDT. This will be measured using peripheral blood analyzed using fluorescence-labelling and flow analysis (FACS) |
Countries
United States
Contacts
CONTACTEdward Maytin, MD, PhD
PRINCIPAL_INVESTIGATOREdward Maytin, MD, PhD
Case Comprehensive Cancer Center, Cleveland Clinic
Outcome results
None listed