Clinical trial NCT05020912: Alteration of the Immune Microenvironment in Basal Cell Carcinoma Following Photodynamic Therapy
Official title: Alteration of the Immune Microenvironment in Basal Cell Carcinoma (BCC) Following Photodynamic Therapy (PDT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Basal Cell Carcinoma
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2021-08-25
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Each participant will serve as their own control - one tumor will be PDT-treated and other left as untreated control
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Time to maximum expression of immune checkpoint molecules
timeFrame: at visit 2 (1-14 days)
measure: Altered expression of immune checkpoint molecules
timeFrame: at visit 2 (1-14 days)
measure: Altered recruitment of different immune cell subtypes in BCC tumor specimens
timeFrame: at visit 2 (1-14 days)
Secondary outcomes:
measure: Proportion of tumor-activated CD8+ T-cells after PDT
timeFrame: at visit 2 (1-14 days)
measure: Rate of protoporphyrin IX (PpIX) accumulation in tumors
timeFrame: Every 30 minutes up to 4 hours
measure: Maximal PpIX levels in tumors
timeFrame: Every 30 minutes up to 4 hours
measure: Change in the color of tumors
timeFrame: at visit 1 (pre PDT) and visit 2 (1-14 days)
measure: Change in the appearance of tumors
timeFrame: at visit 1 (pre PDT) and visit 2 (1-14 days)
measure: Change in the volume of tumors
timeFrame: at visit 1 (pre PDT) and visit 2 (1-14 days)
measure: Distant tumor (abscopal) effects after PDT
timeFrame: at visit 2 (1-14 days)
measure: To determine the relationship of PDT with the expression of immune- and cancer-associated RNA molecules
timeFrame: at visit 1 (pre PDT) and visit 2 (1-14 days)
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic, Case Comprehensive Cancer Center
name: Edward V Maytin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: