Photodynamic Therapy Monitoring for Actinic Keratosis

Overseen By Edward Maytin, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Case Comprehensive Cancer Center

Must not be taking: Topical treatments

Disqualifiers: Pregnancy, Cancer treatment, Photosensitivity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new video device to determine its ability to predict the effectiveness of photodynamic therapy (PDT) for actinic keratosis, which are rough, scaly skin patches caused by sun damage. During the trial, researchers will take images of the skin lesions to monitor the treatment's effectiveness. The trial seeks participants with at least 10 actinic keratosis lesions on their arms or legs and no sensitivity to the treatment ingredients. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop using any topical treatments on your actinic keratoses at least one month before participating. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What prior data suggests that this video device is safe for monitoring actinic keratosis?

Research has shown that photodynamic therapy (PDT) is generally safe for treating skin conditions like actinic keratosis. Studies have found that PDT is effective, with pain being the most common short-term side effect. Patients might experience discomfort during or soon after treatment, but it is usually not dangerous.

In this trial, the treatment combines PDT with a cream called aminolevulinate and red light. The safety of this combination is also positive. Many people tolerate it well, though some might feel stinging or burning, especially on sensitive areas like the face. This sensation occurs in about half of the patients treated on the face and scalp, and less often on other body parts, like the arms.

Overall, the treatment is well-tolerated and considered safe for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Photodynamic therapy (PDT) is unique because it combines a topical drug called aminolevulinate with red light illumination to treat actinic keratosis. Unlike other treatments like cryotherapy or topical chemotherapies, PDT specifically uses light to activate the drug, which then targets and destroys abnormal skin cells. Researchers are excited about PDT because it offers a targeted, non-invasive approach with minimal damage to surrounding healthy tissue, potentially leading to better cosmetic outcomes and fewer side effects.

What evidence suggests that this video device is effective for monitoring actinic keratosis during photodynamic therapy?

Research shows that photodynamic therapy (PDT), which participants in this trial will receive, effectively treats actinic keratosis, a skin condition caused by sun damage. Studies have found that PDT clears skin spots up to 14% better than treatments like freezing (cryotherapy). It boasts high success rates, with 70–90% of spots clearing after treatment, and generally leaves the skin looking good afterward. This treatment uses a special cream called aminolevulinate and red light to target and destroy damaged skin cells. Overall, PDT is a strong option for managing actinic keratosis. ^{2 6 7 8 9}

Who Is on the Research Team?

Edward Maytin, MD, PhD

Principal Investigator

Cleveland Clinic, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals who can consent to treatment, have at least 10 Actinic Keratoses (AK) lesions on their arms or legs, and two AK lesions close enough to be imaged together. Pregnant or nursing women, those using topical treatments for AK within the last month, with photosensitivity diseases like porphyria cutanea tarda, allergies to study materials, or undergoing other cancer treatments are excluded.

Inclusion Criteria

Participants must be able to understand and are willing to sign a written informed consent document

I have over 10 skin lesions on my arms or legs, with at least two close together.

Exclusion Criteria

I have stopped any skin treatments for my condition at least a month ago.

I am not and will not become pregnant or breastfeed during the study.

I have a history of a condition that makes my skin sensitive to light.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard red light PDT treatment with topical aminolevulinate. Photos and videos are taken to monitor treatment progress.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Remaining lesions are counted.

3 months

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Photodynamic therapy (PDT)
• Red light illumination

Trial Overview The study tests a new video device that captures images of skin lesions during photodynamic therapy (PDT) for actinic keratoses. It involves applying a topical drug called Aminolevulinate followed by red light illumination to see if the device can predict treatment success.

How Is the Trial Designed?

Group I: Standard PDT + topical aminolevulinate + red light illumination Experimental Treatment 3 Interventions

Standard PDT using topical aminolevulinate followed by red light illumination for actinic keratosis. A region of interest (ROI) on the skin of the arms, hands, legs, or feet will be selected for monitoring. This ROI will be marked and baseline measurements will be taken. The topical drug Levulan (ALA) will be applied to the ROI and other areas being treated, and covered with plastic wrap. Prior to red light illumination, post topical measurements and baseline values will be performed to measure PpIX and sO2. Red light illumination will follow, and sO2 phosphorescence will be recorded continuously from the ROI. After, a post-PpIX measurement will be taken.

Photodynamic therapy (PDT) is already approved in United States, European Union for the following indications:

Approved in United States as Photodynamic therapy for:

• Actinic keratosis
• Basal cell skin cancer
• Esophageal cancer
• Non-small cell lung cancer
• Squamous cell skin cancer (Stage 0)
• Barrett esophagus
• Advanced cutaneous T-cell lymphoma

Approved in European Union as Photodynamic therapy for:

• Actinic keratosis
• Basal cell skin cancer
• Esophageal cancer
• Non-small cell lung cancer
• Squamous cell skin cancer (Stage 0)
• Barrett esophagus

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

In a study of 357 patients treated with photodynamic therapy (PDT) for actinic keratoses, 17 patients developed squamous cell carcinoma (SCC) at the treatment site, indicating a potential risk of malignant transformation associated with PDT.

Patients with multiple risk factors for non-melanoma skin cancer (NMSC) showed a higher incidence of SCC after PDT, suggesting that these individuals may require more frequent follow-ups to monitor for potential cancer development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methyl-aminolevulinic acid photodynamic therapy for actinic keratoses: a useful treatment or a risk factor? A retrospective study. Bardazzi, F., Loi, C., Magnano, M., et al.[2018]

In a study of 80 patients, photodynamic therapy (PDT) using methyl aminolevulinate (MAL) cream resulted in a significantly higher complete response rate for actinic keratoses compared to placebo, with 89% of lesions responding to treatment versus 38% for placebo.

The cosmetic outcomes were also very positive, with over 90% of patients treated with MAL reporting excellent or good results, indicating that this treatment is not only effective but also well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: results of a prospective randomized multicenter trial. Pariser, DM., Lowe, NJ., Stewart, DM., et al.[2018]

In a study involving 131 patients with actinic keratoses, photodynamic therapy (PDT) using topical methyl aminolevulinate (MAL) and LED light was found to be significantly more effective than placebo, achieving an 83.3% complete response rate for lesions compared to only 28.7% for the placebo group.

The treatment was well-tolerated, demonstrating that MAL PDT is a promising option for effectively treating multiple actinic keratoses on the face and scalp.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical methyl aminolevulinate photodynamic therapy using red light-emitting diode light for multiple actinic keratoses: a randomized study. Szeimies, RM., Matheson, RT., Davis, SA., et al.[2019]

In a study of 62 patients treated with methyl aminolevulinate-photodynamic therapy (MAL-PDT) for actinic keratosis (AKs), 175 out of 178 lesions showed a complete response after 3 years, indicating high efficacy of this treatment.

The study reported a low recurrence rate, with only 8 recurrences after the first treatment and 2 after the second, and only 2 cases of malignant transformation to squamous cell carcinoma, suggesting that MAL-PDT is a safe and effective long-term option for managing AKs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy in the management of actinic keratosis: Retrospective evaluation of outcome. Jerjes, W., Hamdoon, Z., Abdulkareem, AA., et al.[2017]

In a study involving 22 patients with actinic keratoses, applying a superpotent corticosteroid (clobetasol propionate) before and after photodynamic therapy (PDT) significantly reduced treatment-induced erythema, which is a common side effect.

The use of the corticosteroid did not affect the overall effectiveness of PDT, suggesting it can be a simple method to improve patient comfort during treatment without compromising results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical corticosteroid reduces inflammation without compromising the efficacy of photodynamic therapy for actinic keratoses: a randomized clinical trial. Wiegell, SR., Petersen, B., Wulf, HC.[2016]

Occlusive application of 5-aminolevulinic acid (ALA) during photodynamic therapy (PDT) significantly improves the clearance rates of actinic keratoses (AK) compared to non-occlusive application, with 88.4% clearance at 3 months for occlusive versus 58.1% for non-occlusive.

However, the occlusive method is associated with higher pain levels and increased skin phototoxicity, indicating a trade-off between efficacy and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of occlusive vs non-occlusive application of 5-aminolevulinic acid (BF-200 ALA) on the efficacy and tolerability of photodynamic therapy for actinic keratosis on the scalp and face: A prospective within-patient comparison trial. Meierhofer, C., Silic, K., Urban, MV., et al.[2021]

This study developed new radiometric methods to accurately calculate the effective fluence and dose of photosensitizers at different skin depths during photodynamic therapy (PDT) for actinic keratosis, comparing red, blue, and daylight sources.

Results showed that while the red-lamp provided the highest effective fluence at depth, the blue-lamp had the highest effective irradiance, highlighting the importance of considering depth-specific fluence for optimizing PDT treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective fluence and dose at skin depth of daylight and lamp sources for PpIX-based photodynamic therapy. Ruiz, AJ., LaRochelle, EPM., Samkoe, KS., et al.[2023]

Photodynamic therapy (PDT) has been proven effective and safe for treating actinic keratosis in large clinical trials conducted over the past five years.

Recent evidence highlights new challenges in PDT, including managing field cancerization and fluorescence diagnosis, as well as the need for more comparative studies with other treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Studies of methyl aminolevulinate photodynamic therapy for actinic keratosis]. Fernández-Guarino, M., Harto, A., Jaén, P.[2016]

Photodynamic therapy (PDT) is effective for treating actinic keratoses (AKs) and offers better cosmetic outcomes and patient satisfaction compared to other treatments like imiquimod and 5-fluorouracil, based on a comprehensive review of the literature.

Daylight PDT is preferred by patients over traditional light sources due to its better tolerability, and it shows promising results even as a preventive treatment for high-risk individuals, such as organ transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic Therapy for Field Cancerization in the Skin: Where Do We Stand? Bakirtzi, K., Papadimitriou, I., Vakirlis, E., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9332024/

The Role and Effectiveness of Photodynamic Therapy on ... Studies have shown that all treatments (DL-PDT, C-PDT, BF-200 ALA, MAL-PDT) are effective in patients with AK and can be clinically applied. In ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666328725000227

Expert consensus-based recommendations on the use of ... This modified Delphi method consensus group has established 55 statements surrounding the use of photodynamic therapy in treating actinic keratoses.

3. jamanetwork.com jamanetwork.com/journals/jamadermatology/fullarticle/1899263

Efficacy of Photodynamic Therapy vs Other Interventions in ... Photodynamic therapy has a 14% better chance of complete lesion clearance at 3 months after treatment than cryotherapy for thin AKs on the face and scalp.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37134239/

A Meta-Analysis Update of Randomized Controlled Trials Compared with other methods, PDT is significantly more effective for AK with excellent cosmetic results and reversible adverse effects.

5. rdw.rowan.edu rdw.rowan.edu/stratford_research_day/2025/may1/164/

Photodynamic Therapy vs. 5-Fluorouracil for Field-Directed ... RESULTS: PDT demonstrated high clearance rates (70–90%) and excellent cosmetic results, especially in sensitive or extensive areas. Its major ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5874669/

Early and Late Onset Side Effects of Photodynamic Therapy PDT can be considered an effective and safe treatment options for NMSC. Pain is the most clinically relevant short-term complication, that also ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03805737

Indoor Daylight Photo Dynamic Therapy for Actinic Keratosis The primary aim of this study is to study if indoor daylight PDT can be as effective as regular lamp light PDT. This study can be confounded by the amount of ...

8. mayoclinic.org mayoclinic.org/tests-procedures/photodynamic-therapy/about/pac-20385027

Photodynamic therapy After light activation, however, the photosensitizer becomes toxic to the targeted tissue.

9. mdpi.com mdpi.com/2072-6694/17/6/1050

Daylight Photodynamic Therapy for Actinic Keratosis and ... The conventional PDT (cPDT) has already been proven a safe and effective method to treat non-hyperkeratotic actinic keratosis and field cancerization.