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

March 13, 2026 updated by: Case Comprehensive Cancer Center

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

54

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Edward Maytin, MD, PhD
  • Phone Number: (216) 346-6022
  • Email: maytine@ccf.org

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute
        • Contact:
          • Edward Maytin, MD, PhD
        • Principal Investigator:
          • Edward Maytin, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Procedure: Mohs 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.
Experimental: 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.
Procedure: Mohs 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.
Dietary supplement: Vitamin 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.
Other: Photodynamic therapy (PDT)
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.
Placebo Comparator: 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.
Procedure: Mohs 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.
Other: Photodynamic therapy (PDT)
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.
Other: Placebo
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Expression of immune checkpoint molecules
Time Frame: 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.
At time of Mohs surgery or ED&C, up to Day 20

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ratio of cytotoxic T cells to regulatory T cells
Time Frame: 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).
At time of Mohs surgery or ED&C, up to Day 20
Ratio of M1 macrophages to M2 macrophages
Time Frame: 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).
At time of Mohs surgery or ED&C, up to Day 20
Proportion of tumor-activated CD8+ T-cells in circulating T-cells
Time Frame: 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)
At time of Mohs surgery or ED&C, up to Day 20

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Case Comprehensive Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Edward Maytin, MD, PhD, Case Comprehensive Cancer Center, Cleveland Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

August 1, 2027

Study Registration Dates

First Submitted

November 17, 2025

First Submitted That Met QC Criteria

November 17, 2025

First Posted (Actual)

November 21, 2025

Study Record Updates

Last Update Posted (Actual)

March 17, 2026

Last Update Submitted That Met QC Criteria

March 13, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CASE12Z25
  • 5P01CA084203 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All IPD that underlie results in publication

IPD Sharing Time Frame

6 months after publication

IPD Sharing Access Criteria

Request to the PI

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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