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| ID | Type | Description | Link |
|---|---|---|---|
| 5P01CA084203 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: Participants donate discarded tissue for research (No VitD/Placebo + no PDT) | Other | 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. |
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| Arm 2: VitD + PDT prior to Mohs surgery or ED&C | Experimental | 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. |
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| Arm 3: Placebo + PDT prior to Mohs surgery or ED&C | Placebo Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vitamin D (VitD) | Dietary Supplement | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Expression of immune checkpoint molecules | 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. | At time of Mohs surgery or ED&C, up to Day 20 |
| Measure | Description | Time Frame |
|---|---|---|
| Ratio of cytotoxic T cells to regulatory T cells | 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). | At time of Mohs surgery or ED&C, up to Day 20 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Edward Maytin, MD, PhD | Contact | (216) 346-6022 | maytine@ccf.org |
| Name | Affiliation | Role |
|---|---|---|
| Edward Maytin, MD, PhD | Case Comprehensive Cancer Center, Cleveland Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute | Recruiting | Cleveland | Ohio | 44106 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17190630 | Background | Braathen LR, Szeimies RM, Basset-Seguin N, Bissonnette R, Foley P, Pariser D, Roelandts R, Wennberg AM, Morton CA; International Society for Photodynamic Therapy in Dermatology. Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: an international consensus. International Society for Photodynamic Therapy in Dermatology, 2005. J Am Acad Dermatol. 2007 Jan;56(1):125-43. doi: 10.1016/j.jaad.2006.06.006. | |
| 41070141 | Background |
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All IPD that underlie results in publication
6 months after publication
Request to the PI
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Masking only applies to Arms 2 and 3, not Arm 1.
| Placebo | Other | 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. |
|
| Photodynamic therapy (PDT) | Other | 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. |
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| Mohs surgery or electrodessication & curettage (ED&C) (standard of care) | Procedure | 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. |
|
| Ratio of M1 macrophages to M2 macrophages |
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). |
| At time of Mohs surgery or ED&C, up to Day 20 |
| Proportion of tumor-activated CD8+ T-cells in circulating T-cells | 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) | At time of Mohs surgery or ED&C, up to Day 20 |
| Pogue BW, Chen B, Ochoa MI, Petusseau A, Liu A, Gibson ALF, Maytin EV, Wilson BC. Emerging uses of 5-aminolevulinic-acid-induced protoporphyrin IX in medicine: a review of multifaceted, ubiquitous, molecular diagnostic, therapeutic, and theranostic opportunities. J Biomed Opt. 2025 Dec;30(Suppl 3):S34112. doi: 10.1117/1.JBO.30.S3.S34112. Epub 2025 Oct 8. |
| 40616218 | Background | Ortenzio MP, Anand S, Travers JB, Maytin EV, Rohan CA. Immunomodulatory effects of photodynamic therapy for skin cancer: Potential strategies to improve treatment efficacy and tolerability. Photochem Photobiol. 2026 May-Jun;102(3):533-547. doi: 10.1111/php.70008. Epub 2025 Jul 4. |
| 38281610 | Background | Anand S, Shen A, Cheng CE, Chen J, Powers J, Rayman P, Diaz M, Hasan T, Maytin EV. Combination of vitamin D and photodynamic therapy enhances immune responses in murine models of squamous cell skin cancer. Photodiagnosis Photodyn Ther. 2024 Feb;45:103983. doi: 10.1016/j.pdpdt.2024.103983. Epub 2024 Jan 27. |
| 32077114 | Background | Maytin EV, Hasan T. Vitamin D and Other Differentiation-promoting Agents as Neoadjuvants for Photodynamic Therapy of Cancer. Photochem Photobiol. 2020 May;96(3):529-538. doi: 10.1111/php.13230. Epub 2020 Apr 15. |
| 21807844 | Background | Anand S, Wilson C, Hasan T, Maytin EV. Vitamin D3 enhances the apoptotic response of epithelial tumors to aminolevulinate-based photodynamic therapy. Cancer Res. 2011 Sep 15;71(18):6040-50. doi: 10.1158/0008-5472.CAN-11-0805. Epub 2011 Aug 1. |
| 36813159 | Background | Bullock TA, Mack JA, Negrey J, Kaw U, Hu B, Anand S, Hasan T, Warren CB, Maytin EV. Significant Association of Poly-A and Fok1 Polymorphic Alleles of the Vitamin D Receptor with Vitamin D Serum Levels and Incidence of Squamous Cutaneous Neoplasia. J Invest Dermatol. 2023 Aug;143(8):1538-1547. doi: 10.1016/j.jid.2023.01.028. Epub 2023 Feb 20. |
| 40633744 | Background | Maytin EV, Zeitouni NC, Updyke A, Negrey JT, Shen AS, Heusinkveld LE, Mack JA, Hu B, Anand S, Maytin TA, Giostra L, Bullock T, Warren CB, Hasan T. High-dose oral vitamin D in combination with photodynamic therapy can accelerate the clearance rate of basal cell carcinoma: A randomized clinical trial. Photodiagnosis Photodyn Ther. 2025 Oct;55:104704. doi: 10.1016/j.pdpdt.2025.104704. Epub 2025 Jul 7. |
| 38310633 | Background | Anand S, Hasan T, Maytin EV. Treatment of nonmelanoma skin cancer with pro-differentiation agents and photodynamic therapy: Preclinical and clinical studies (Review). Photochem Photobiol. 2024 Nov-Dec;100(6):1541-1560. doi: 10.1111/php.13914. Epub 2024 Feb 4. |
| ID | Term |
|---|---|
| D002280 | Carcinoma, Basal Cell |
| D002294 | Carcinoma, Squamous Cell |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D018295 | Neoplasms, Basal Cell |
| D018307 | Neoplasms, Squamous Cell |
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| ID | Term |
|---|---|
| D014807 | Vitamin D |
| D010778 | Photochemotherapy |
| D015580 | Mohs Surgery |
| D003475 | Curettage |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D012632 | Secosteroids |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D003131 | Combined Modality Therapy |
| D013812 | Therapeutics |
| D004358 | Drug Therapy |
| D010789 | Phototherapy |
| D008866 | Microsurgery |
| D013514 | Surgical Procedures, Operative |
| D062109 | Dermatologic Surgical Procedures |
| D019651 | Plastic Surgery Procedures |
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
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