Basal Cell CarcinomaPhase 2NCT05020912
Alteration of the Immune Microenvironment in Basal Cell Carcinoma Following Photodynamic Therapy
A Phase 2 study testing ALA and PDT in people with Basal Cell Carcinoma, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Basal Cell Carcinoma
- What is being tested?
- ALA and PDT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Dec 2021to Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Cleveland Clinic, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
Official title: Alteration of the Immune Microenvironment in Basal Cell Carcinoma (BCC) Following Photodynamic Therapy (PDT)
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.
Read the 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
- Conditions
- Basal Cell Carcinoma
- Being tested
- ALA, PDT
- Medical subject headings
- Carcinoma, Basal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALADrug
Also called Levulan
At first visit, ALA applied to one BCC lesion
PDTProcedure or surgery
PDT with blue light (for 30 min (~20 mJ/cm2))
| Study group | Role | What they receive |
|---|---|---|
| Photodynamic therapy (PDT) | Experimental | 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 Receives: Drug: ALA; Procedure: PDT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to maximum expression of immune checkpoint molecules
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
Measured: at visit 2 (1-14 days)
Altered expression of immune checkpoint molecules
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)
Measured: at visit 2 (1-14 days)
Altered recruitment of different immune cell subtypes in BCC tumor specimens
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+).
Measured: at visit 2 (1-14 days)
Secondary outcomes (8)
Proportion of tumor-activated CD8+ T-cells after PDT
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.
Measured: at visit 2 (1-14 days)
Rate of protoporphyrin IX (PpIX) accumulation in tumors
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.
Measured: Every 30 minutes up to 4 hours
Maximal PpIX levels in tumors
Maximal PpIX levels in tumors, assessed via noninvasive measurements of PpIX fluorescence using a dosimeter
Measured: Every 30 minutes up to 4 hours
Change in the color of tumors
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.
Measured: at visit 1 (pre PDT) and visit 2 (1-14 days)
Change in the appearance of tumors
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.
Measured: at visit 1 (pre PDT) and visit 2 (1-14 days)
Change in the volume of tumors
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.
Measured: at visit 1 (pre PDT) and visit 2 (1-14 days)
Distant tumor (abscopal) effects after PDT
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.
Measured: at visit 2 (1-14 days)
To determine the relationship of PDT with the expression of immune- and cancer-associated RNA molecules
Determine whether PDT is associated with altered expression of immune- and cancer-associated RNA transcripts in BCC using NanoString nCounter.
Measured: at visit 1 (pre PDT) and visit 2 (1-14 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2021
- Study start13 Dec 2021
- Primary completionSep 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Basal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Each participant will serve as their own control - one tumor will be PDT-treated and other left as untreated control
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Edward V Maytin, MD, PhD, Principal investigator, Cleveland Clinic, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05020912
- Sponsor's protocol ID
- CASE2621
- Status last verified
- May 2026
- First submitted
- 19 Aug 2021
- Last updated
- 1 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie results in publication
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Alteration of the Immune Microenvironment in Basal Cell Carcinoma (BCC) Following Photodynamic Therapy (PDT)
- ClinicalTrials.gov ID
- NCT05020912
- Acronym / sponsor ID
- CASE2621
- Conditions
- Basal Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 13 Dec 2021 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 25 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Each participant will serve as their own control - one tumor will be PDT-treated and other left as untreated control
| Arm | Type | Receives |
|---|---|---|
| Photodynamic therapy (PDT) | Experimental | Drug: ALA, Procedure: PDTEach 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ALAAlso: LevulanAt first visit, ALA applied to one BCC lesion | Drug | Photodynamic therapy (PDT) |
| PDTPDT with blue light (for 30 min (~20 mJ/cm2)) | Procedure or surgery | Photodynamic therapy (PDT) |
Primary outcome
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
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)
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+).
8 secondary outcomes
Proportion of tumor-activated CD8+ T-cells after PDT
Time frame: at visit 2 (1-14 days)
Rate of protoporphyrin IX (PpIX) accumulation in tumors
Time frame: Every 30 minutes up to 4 hours
Maximal PpIX levels in tumors
Time frame: Every 30 minutes up to 4 hours
Change in the color of tumors
Time frame: at visit 1 (pre PDT) and visit 2 (1-14 days)
Change in the appearance of tumors
Time frame: at visit 1 (pre PDT) and visit 2 (1-14 days)
Change in the volume of tumors
Time frame: at visit 1 (pre PDT) and visit 2 (1-14 days)
Distant tumor (abscopal) effects after PDT
Time frame: at visit 2 (1-14 days)
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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2026.
- Individual participant dataSharing planned: Yes. All IPD that underlie results in publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edward V Maytin, MD, PhD principal investigator
Cleveland Clinic, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ALA and PDT in people with Basal Cell Carcinoma, run by Case Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to maximum expression of immune checkpoint molecules (time frame: at visit 2 (1-14 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2026.