SUV PDL1/PD1 in Sun Damaged & Sun Protected Human Skin of Participants
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age40+
SponsorUniversity of Arizona
About this trial
The purpose of this research study is to look at how the proteins and genes in people's skin change when they're exposed to simulated sunlight. The researchers want to see if there are differences between people who've had skin cancer and those who haven't despite having a similar type of skin and history of sun exposure. Since this study is designed to simulate sun exposure to small areas of skin, mild to moderate sunburn and tanned spots at the site of the simulated sunlight exposure is a risk. In addition to simulated sun exposure, patients will also have four 6 mm punch skin biopsies performed. Brief discomfort may be felt when the local painkiller (lidocaine) is injected prior to skin biopsies; however, it is usually minimal. Participation in the study involves 4 visits to the clinic over the course of 4 weeks. Each visit will take no longer than 90 minutes.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Healthy individuals 40 years of age or older. Note: When the two groups are paired, participants will be balanced within 5 years of age. Ex. From 2.5 years younger or 2.5 years older.
Individuals with moderate or severe photodamage of the skin on the forearms and Fitzpatrick skin type II or III (21 CFR 352.72).
Individuals with a history of two or more cSCCs within the past 5 years (maximum of 23 enrolled) or individuals with no history of cSCC (maximum of 23 enrolled)
Females of childbearing potential will need to undergo a pregnancy test at the enrollment visit, after administration of the ICF (informed consent form) and before exposure to solar simulated light (SSL) Premenopausal female subjects must use an effective method of birth control (such as oral contraceptives, consistent use of barrier contraceptives, IUD (intrauterine device), or other proven method of birth control) during study participation. For the purposes of this study, a woman will be considered postmenopausal if any of the following criteria are met: (1) she has had prior bilateral oophorectomy; (2) she is over the age of 60 years; or (3) she is under the age of 60 years and has not had a menstrual period in 12 or more months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression.
Disqualifiers
Individuals with any inflammation or irritation of the skin at the test areas, or any skin conditions felt by the study healthcare provider to contraindicate enrollment. This includes, but is not limited to, psoriasis or atopic dermatitis within the test areas. (Test area is defined as the 6 mm areas of skin that is exposed to SSL and will be biopsied.)
Individuals with a history of untreated skin cancer or melanocytic lesions in the test areas are ineligible. History of such conditions at a body site other than the test areas is not exclusionary if in the opinion of the study healthcare provider it will not pose a risk to the subject.
Individuals who have had invasive cancer, chemotherapy or radiation therapy within five years of study enrollment
Individuals who are immunosuppressed by virtue of medication or disease. This includes AIDS patients, subjects taking oral steroids, and subjects on immunosuppressants/immunomodulators (cyclosporine, chemotherapeutic agents, or biologic therapy), as determined by the examining study healthcare provider
Trial design
Design model
Single group
Treatments tested in this trial
Solar Simulated Light
Other interventionAcute SSL will be delivered to sun damaged skin at a rate of two-times the minimal erythema dose of each individual subject. Minimal erythema dose is defined as the smallest dose of energy necessary to produce confluent erythema with four distinct borders at 22-26 hours post-exposure.
Treatment groups
46 Participants
are divided into 2 treatment groupsGroup A: Cohort A - history of > 2 Cutaneous squamous cell carcinoma (cSCC)Other 1 intervention
Group B: Cohort B - no history of cSCCOther 1 intervention
Trial outcomes
Primary outcomes
1
To assess PD-L1 protein expression levels in the epidermal keratinocytes of subjects with and without a history of cutaneous squamous cell skin cancer.
The primary objective will be the relative increase in PD-L1 protein expression levels in the epidermal keratinocytes of subjects in two risk cohorts (Cohort A (history of \> 2 cSCC) and Cohort B (no history of cSCC)) after acute solar simulated light treatment compared to unexposed skin within the same subject. Proteomic evaluation will be performed by reverse phase protein microarray and confirmatory IHC (immunohistochemistry) stain.
Time frame
Changes from baseline (pre-SSL exposure) to post-SSL exposure (at 24 hour post-exposure).Secondary outcomes
1
Evaluation of CD70/CD27 protein expression analysis
Reverse phase protein microarray will be implemented to evaluate changes in CD70/CD27 protein expression and immunohistochemistry assays will analyze changes in these signaling pathways over time.
Time frame
Changes from baseline (pre-SSL exposure) to post-SSL exposure (at 24 hour post-exposure).2
Spatial genomic assessment through whole transcriptomic analysis
Nanostring DSP (Digital Spatial Profiling). Whole transcriptomic analysis will assess these markers as well as query signaling pathways which may be differentially affected by UV in each group. The research team will perform NanoString spatial whole transcriptomic analysis on SD (sun damaged) skin samples in the 20 participants from each cohort by evaluating both pre- and post- SSL exposure, resulting in 2 matched pairs per study subject. The research team will also use DermTech RNA-seq for skin sampling and gene expression analysis on a subset of sun damaged skin samples.
Time frame
Changes from baseline (pre-SSL exposure) to post-SSL exposure (at 24 hour post-exposure).3
High dimensional data analysis
The objective is to integrate the proteomic and genomic data to evaluate possible synergistic relationship between them in describing the risk of cSCC based on PD-L1/PD1 and other co-expressed genes/protein expression.
Time frame
Changes from baseline (pre-SSL exposure) to post-SSL exposure (at 24 hour post-exposure).Sponsors and contacts
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University of Arizona
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Source ClinicalTrials.gov