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

Case Comprehensive Cancer Center (Case CCC)

Status and phase: Enrolling; Phase 2

Conditions: Basal Cell Carcinoma

Treatments: Procedure: PDT; Drug: ALA

Study type: Interventional

Funder types: Other

Identifiers

NCT05020912

CASE2621

Details and patient eligibility

About

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.

Full description

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

Enrollment: 28 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adults scheduled to undergo Mohs surgery within the Dermatologic Surgery unit of the Department of Dermatology, Cleveland Clinic
• Must have at least one BCC tumor eligible for removal by surgical excision
• Men and women of any ethnic group are eligible
• Must provide informed consent to participate

Exclusion criteria

• Pregnant or breastfeeding
• Currently being treated for other cancers with medical or radiation therapy
• Known hypersensitivity to 5-aminolevulinic acid (ALA)
• History of a photosensitivity disease, e.g.,porphyria cutanea tarda

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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28 participants in 1 patient group

Photodynamic therapy (PDT)

Experimental group

Description:

Each participant will serve as their own control, receiving PDT for one tumor, no PDT for the second tumor (untreated control). Visit 1: * Informed consent * Blood draw * Lesion(s) Photographed * (ALA) applied for4 hours * PpIX measured in lesions (PpIX buildup monitored every 30 minutes over a 4 h period) * PDT with blue light Visit 2 (scheduled for within one of the following time intervals: 1-3 days, 4-7 days, or 8-14 days post-PDT): * Blood draw * Lesion(s) Photographed * Mohs surgery * After procedure, excess frozen BCC tissue will be saved for analysis

Treatment:

Drug: ALA

Procedure: PDT