Vitamin D Effects on Immune Microenvironment of Nonmelanoma Skin Cancer After Photodynamic Therapy (PDT)

NCT07241585 | Not Yet Recruiting DMC

• 2 other identifiers: CASE12Z255P01CA084203
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Nonmelanoma Skin Cancer; Basal Cell Carcinoma; Squamous Cell Carcinoma

Keywords

Mohs surgery; Electrodessication & curettage; ED&C; Photodynamic therapy; PDT; Vitamin D

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• 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

Study Arms (3)

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.

Procedure: Mohs surgery or electrodessication & curettage (ED&C) (standard of care)

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.

Dietary Supplement: Vitamin D (VitD); Other: Photodynamic therapy (PDT); Procedure: Mohs surgery or electrodessication & curettage (ED&C) (standard of care)

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.

Other: Placebo; Other: Photodynamic therapy (PDT); Procedure: Mohs surgery or electrodessication & curettage (ED&C) (standard of care)

Interventions

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.

Arm 2: VitD + PDT prior to Mohs surgery or ED&C

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.

Arm 3: Placebo + PDT prior to Mohs surgery or ED&C

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.

Arm 2: VitD + PDT prior to Mohs surgery or ED&C; Arm 3: Placebo + PDT prior to Mohs surgery or ED&C

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.

Arm 1: Participants donate discarded tissue for research (No VitD/Placebo + no PDT); Arm 2: VitD + PDT prior to Mohs surgery or ED&C; Arm 3: Placebo + PDT prior to Mohs surgery or ED&C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute

Cleveland, Ohio, 44106, United States

Location

Related Publications (9)

• 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.

  PMID: 17190630 BACKGROUND

• 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.

  PMID: 41070141 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. 2025 Jul 4. doi: 10.1111/php.70008. Online ahead of print.

  PMID: 40616218 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.

  PMID: 38281610 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.

  PMID: 32077114 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.

  PMID: 21807844 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.

  PMID: 36813159 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.

  PMID: 40633744 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.

  PMID: 38310633 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Basal Cell; Carcinoma, Squamous Cell

Interventions

Vitamin D; Photochemotherapy; Mohs Surgery; Curettage; Standard of Care

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Basal Cell; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Combined Modality Therapy; Therapeutics; Drug Therapy; Phototherapy; Microsurgery; Surgical Procedures, Operative; Dermatologic Surgical Procedures; Plastic Surgery Procedures; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Edward Maytin, MD, PhD

  Case Comprehensive Cancer Center, Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Edward Maytin, MD, PhD

CONTACT

(216) 346-6022; maytine@ccf.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Masking only applies to Arms 2 and 3, not Arm 1.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: November 21, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 6 months after publication
• Access Criteria: Request to the PI

Locations

US (1)