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NCT Number: NCT05020912

Alteration of the Immune Microenvironment in Basal Cell Carcinoma Following Photodynamic Therapy

The purpose of this study is to better understand the immune response to basal cell carcinoma (BCC) treated with Photodynamic Therapy (PDT) in order to develop new methods of treating BCC. Previous research suggests that PDT alters the immune response, possibly in a way that could promote better tumor clearance when combined with other treatments. Overall, participation in this study will help the study team better understand the anti-tumor immune response when BCC is treated with PDT.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Cleveland Clinic, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

About this study

PDT is a technique that works by combining a photosensitizing topical agent and an intense light to kill tumor cells. PDT is not currently approved for the treatment of BCC by the Food and Drug Administration (FDA), although it is approved for that purpose in many European countries.

This is an internally (bilaterally) controlled trial that will enroll 24 participants with biopsy-proven BCC who are planning to undergo tumor removal via Mohs surgery. Within this cohort, one tumor will be PDT-treated and the other left as an untreated control. This study is also a cohort-controlled trial, because discarded tissue from fully de-identified Mohs participants will be analyzed after routine Mohs surgery, in order to establish the baseline variability in tumor-infiltrating immune cell parameters in non-PDT-treated participants.

The objectives of this study are:

To determine the time to maximum expression of immune checkpoint molecules in BCC tumors and peri-tumoral stroma after PDT, as compared to untreated tumors.

To determine the ratio of cytotoxic T cells to regulatory T cells in BCC tumors and peri-tumoral stroma after PDT, as compared to untreated tumors.

To determine whether circulating T-cells, collected from patients' peripheral blood, sampled before and after PDT treatment of a BCC tumor, show a higher proportion of tumor-activated CD8+ T-cells after PDT. The hypothesis is that PDT of the localized tumor will trigger a systemic anti-tumor immune effect.

To determine the rate of protoporphyrin IX (PpIX) accumulation and maximal PpIX levels.in tumors To determine the rate of production and maximal levels of singlet oxygen (O2) produced during blue light exposure To assess change in the volume, color, and appearance of tumors at the Mohs surgery visit compared to the PDT visit To assess for distant tumor (abscopal) effects after PDT

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Must be an adult parcticpant (> 18 yrs) who is scheduled to undergo BCC surgery (via Mohs surgery, ED&C, or standard elliptical excision) within the Dermatologic Surgery unit of the Department of Dermatology, Cleveland Clinic.
  • Must have at least one BCC tumor eligible for surgical removal
  • Participants of any ethnic group are eligible for this trial.
  • Must provide informed consent to participate in the trial.

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

Treatment and study plan

ALA

Drug

At first visit, ALA applied to one BCC lesion

Other names: Levulan

PDT

Procedure

PDT with blue light (for 30 min (~20 mJ/cm2))

Primary outcomes

  1. Time to maximum expression of immune checkpoint molecules

    Time frame: at visit 2 (1-14 days)

    Time (days) to maximum expression of immune checkpoint molecules in BCC tumors and peri-tumoral stroma after PDT, as compared to untreated tumors.

    Data from frozen BCC specimens post-PDT by immunostaining the tumor specimens with antibodies against PD-L1, PD-1, CTLA-4 as well as the newer IC molecules TIGIT, TIM-3, and LAG-3

  2. Altered expression of immune checkpoint molecules

    Time frame: at visit 2 (1-14 days)

    Altered expression of immune checkpoint molecules in BCC tumor specimens after PDT.

    Assessed by comparing IC molecule expression in PDT treated and untreated tumors with immunostaining in the tumor specimens with antibodies against PD-L1, PD-1, CTLA-4 as well as the newer IC molecules TIGIT, TIM-3, and LAG-3. (quantifying with immunofluorescence microscope)

  3. Altered recruitment of different immune cell subtypes in BCC tumor specimens

    Time frame: at visit 2 (1-14 days)

    Determine the ratio of cytotoxic T cells to regulatory T cells in BCC tumors and peri-tumoral stroma after PDT, as compared to untreated tumors.

    Measured with specific antibodies against the following markers, to determine the qualitative time course of infiltration by each immune cell populations: Neutrophils (Gr1+ or MPO+); Macrophages(F4/80+); MDSCs (CD33, S100A9); cytotoxicT-cells(CD8+); regulatory T-cells(CD4+,FoxP3+,CD25+, CD127-); NK natural killer cells(CD56+CD16+).

Secondary outcomes

  1. Proportion of tumor-activated CD8+ T-cells after PDT

    Time frame: at visit 2 (1-14 days)

    Difference in CD8 T cells after PDT collected from participants' peripheral blood, sampled before and after PDT treatment of a BCC tumor.

    This data is derived from patient blood samples. Each patient will have two blood draws: at Visit 1 (before PDT, to establish a baseline) and at Visit 2. We will compare the proportion of CD8 T cells after PDT based on when the participant returns (within the 3 time ranges), and a single value (difference in CD8 T cells, measured before and after PDT) will be reported for that patient.

  2. Rate of protoporphyrin IX (PpIX) accumulation in tumors

    Time frame: Every 30 minutes up to 4 hours

    Relative rate of PpIX accumulation in tumors assessed via noninvasive measurements of PpIX fluorescence using a dosimeter.

    PpIX will be measured every 30 minutes during the 4 hour incubation. The purpose is to monitor PDT kinetics. We will measure the level of PpIX at each time point, but the final outcome to report is relative rate of change in fluorescence intensity.

  3. Maximal PpIX levels in tumors

    Time frame: Every 30 minutes up to 4 hours

    Maximal PpIX levels in tumors, assessed via noninvasive measurements of PpIX fluorescence using a dosimeter

  4. Change in the color of tumors

    Time frame: at visit 1 (pre PDT) and visit 2 (1-14 days)

    Change in the color of tumors as reported by the participants at the Mohs surgery visit compared to the PDT visit. Number of participants that report common findings after PDT.

  5. Change in the appearance of tumors

    Time frame: at visit 1 (pre PDT) and visit 2 (1-14 days)

    Change in the appearance of tumors as reported by the participants at the Mohs surgery visit compared to the PDT visit. Number of participants that report common findings after PDT. Appearance as being the shape, texture and overlying skin changes.

  6. Change in the volume of tumors

    Time frame: at visit 1 (pre PDT) and visit 2 (1-14 days)

    Change in the volume of tumors at the Mohs surgery visit compared to the PDT visit.

    Tumor volumes (mm3) will be determined from computerized analysis of 3-D photographs.

  7. Distant tumor (abscopal) effects after PDT

    Time frame: at visit 2 (1-14 days)

    Number and type of immune cell present, expression of immune checkpoint molecules, and tumor-activated CD8 T cells present in blood compared to archived samples that did not receive PDT.

  8. To determine the relationship of PDT with the expression of immune- and cancer-associated RNA molecules

    Time frame: at visit 1 (pre PDT) and visit 2 (1-14 days)

    Determine whether PDT is associated with altered expression of immune- and cancer-associated RNA transcripts in BCC using NanoString nCounter.

Sponsors and collaborators

Lead sponsor

Case Comprehensive Cancer Center

Other

Registry information

Official study title

Alteration of the Immune Microenvironment in Basal Cell Carcinoma (BCC) Following Photodynamic Therapy (PDT)

Important dates

Study start
2021
Primary completion
2027
Study completion
2027
First posted
Aug 25, 2021
Registry last updated
Jun 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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