PDT for Basal Cell Carcinoma

Overseen By Edward Maytin, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Case Comprehensive Cancer Center

Disqualifiers: Pregnant, Other cancers, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the immune system's response to treating basal cell carcinoma (BCC), a common skin cancer, with Photodynamic Therapy (PDT). PDT involves applying a special drug called ALA (Aminolevulinic Acid) to the tumor and activating it with blue light to kill cancer cells. Researchers aim to determine if PDT enhances the body's ability to fight the cancer. This trial may suit individuals with BCC who are scheduled for Mohs surgery at the Cleveland Clinic. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are being treated for other cancers with medical or radiation therapy, you cannot participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Past studies have shown that photodynamic therapy (PDT) using aminolevulinic acid (ALA) safely treats basal cell carcinoma (BCC). Research indicates that PDT is generally well-tolerated, with minor side effects like redness and swelling at the treatment site, which usually resolve on their own.

One study found that using a 10% ALA gel in PDT effectively cleared skin tumors and was safe, with no major problems reported. Another study confirmed that PDT is safe and effective, particularly for superficial basal cell carcinoma (sBCC). Overall, the treatment is gentle on the skin while effectively targeting tumors.

The FDA has approved ALA-PDT for other skin conditions, supporting its safety. This approval suggests it could be safe for treating BCC as well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for basal cell carcinoma, which often involve surgical removal or topical creams like imiquimod and 5-fluorouracil, photodynamic therapy (PDT) with aminolevulinic acid (ALA) offers a different approach. This treatment uses a special light-sensitive drug, ALA, which is applied to the skin and activated by blue light to destroy cancer cells. Researchers are excited about PDT because it targets cancer cells directly while sparing healthy tissue, potentially reducing scarring and recovery time. Additionally, PDT with ALA could provide a non-invasive option, making it especially appealing for patients who want to avoid surgery.

What evidence suggests that PDT might be an effective treatment for basal cell carcinoma?

Research has shown that ALA-PDT (Aminolevulinic Acid-Photodynamic Therapy) effectively treats basal cell carcinoma (BCC), a common skin cancer. One study found that it can accurately remove tumors while preserving important facial features, making it suitable for BCCs in sensitive areas. Other research has highlighted ALA-PDT's success in clearing surface-level BCCs. This treatment uses light to activate a drug that targets and destroys cancer cells. In this trial, each participant will receive PDT for one tumor, while another tumor will remain untreated as a control. Studies have found ALA-PDT to be a promising method for BCC, yielding good medical and cosmetic results. ^{3 4 6 7 8}

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 adults with at least two basal cell carcinoma (BCC) tumors that are scheduled for Mohs surgery at the Cleveland Clinic's Dermatology Department. Participants must consent to join and can be of any ethnic group. Pregnant or breastfeeding individuals, those treated for other cancers, allergic to ALA, or with a photosensitivity disease cannot participate.

Inclusion Criteria

I am scheduled for Mohs surgery at Cleveland Clinic's Dermatology Department.

Must provide informed consent to participate

I belong to any ethnic group.

Exclusion Criteria

Known hypersensitivity to 5-aminolevulinic acid (ALA)

Pregnant or breastfeeding

I am currently receiving treatment for another cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Photodynamic Therapy (PDT) Treatment

Participants receive PDT treatment for one tumor, while the other tumor is left untreated as a control. Activities include informed consent, blood draw, lesion photography, ALA application, PpIX measurement, and PDT with blue light.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in tumor appearance, volume, and immune response. This includes a blood draw, lesion photography, and Mohs surgery.

1-14 days

1 visit (in-person)

Long-term Follow-up

Participants are monitored for distant tumor effects and long-term immune response changes.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ALA

Trial Overview The study aims to understand how Photodynamic Therapy (PDT) using ALA affects the immune response against BCC and could improve tumor removal when combined with other treatments. It will help develop new strategies for treating BCC by studying changes in the immune microenvironment post-PDT.

How Is the Trial Designed?

Group I: Photodynamic therapy (PDT) Experimental Treatment 2 Interventions

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

ALA is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Aminolevulinic Acid for:

• Actinic keratosis
• Basal cell carcinoma
• Squamous cell carcinoma in situ

Approved in United States as Levulan for:

• Actinic keratosis
• Basal cell carcinoma

Approved in Canada as Ameluz for:

• Actinic keratosis

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Published Research Related to This Trial

Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) showed high efficacy in treating both early (stage I) and advanced (stage III) mycosis fungoides, with complete responses observed in both cases after specific light doses.

The study demonstrated that the accumulation and fluorescence of protoporphyrin IX (PP) varied between stages of the disease, indicating that the thickness of lesions affects treatment response, but overall, ALA PDT proved to be an effective treatment option for cutaneous T-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy of cutaneous lymphoma using 5-aminolevulinic acid topical application. Orenstein, A., Haik, J., Tamir, J., et al.[2019]

Aminolevulinic acid photodynamic therapy (ALA-PDT) is a safe and effective noninvasive treatment for superficial basal cell carcinoma (BCC) and Bowen's disease, offering excellent cosmetic results with minimal scarring.

ALA-PDT is not suitable for aggressive BCC subtypes or invasive squamous cell carcinoma, but it may help prevent new skin cancers in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aminolevulinic acid photodynamic therapy for skin cancers. Blume, JE., Oseroff, AR.[2013]

In a study involving four patients with seven superficial basal cell carcinomas (sBCCs), treatment with 5-aminolevulinate (ALA) patches resulted in a complete response for all lesions by week 24, indicating strong efficacy.

The ALA patches demonstrated an excellent safety profile, suggesting they could be a promising treatment option for sBCCs, although they are currently FDA and EMA approved only for grade I to II actinic keratosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy with 5-aminolevulinate patch for the treatment of superficial basal cell carcinomas. De Luca, EV., Tambone, S., Catapano, S., et al.[2021]

In a study of 16 patients treated with methyl aminolevulinate photodynamic therapy for eyelid basal cell carcinoma, 82% achieved complete clinical recovery after 5 years, indicating high efficacy for this treatment.

The therapy was well-tolerated with minimal side effects, making it a promising nonsurgical option for patients who cannot undergo surgery due to health concerns or unclear tumor locations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy using methyl aminolevulinate acid in eyelid basal cell carcinoma: a 5-year follow-up study. Puccioni, M., Santoro, N., Giansanti, F., et al.[2018]

In a study involving 54 patients with 95 non-aggressive basal cell carcinomas (BCCs), photodynamic therapy (PDT) using low-concentration hexyl aminolevulinate (HAL) showed similar histological clearance rates (87.9%) compared to methyl aminolevulinate (MAL) (93.8%) and 5-aminolevulinic acid nanoemulsion (BF-200ALA) (90.9%), indicating HAL is an effective alternative.

All treatment options (HAL, MAL, and BF-200 ALA) demonstrated comparable tolerability in terms of pain, post-treatment reactions, and cosmetic outcomes, suggesting that HAL can be a safe and effective choice for PDT in treating BCCs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hexyl aminolevulinate, 5-aminolevulinic acid nanoemulsion and methyl aminolevulinate in photodynamic therapy of non-aggressive basal cell carcinomas: A non-sponsored, randomized, prospective and double-blinded trial. Salmivuori, M., Grönroos, M., Tani, T., et al.[2021]

Photodynamic therapy using delta-aminolevulinic acid (ALA-PDT) showed an 86% complete response rate for superficial basal cell carcinomas (BCC) but only a 54% response rate for superficial squamous cell carcinomas (SCC) among 47 patients over a follow-up period of up to 60 months.

Despite the initial high response rates, the long-term recurrence rates were concerning, with 44% for BCC and 69% for SCC, indicating that ALA-PDT may not provide lasting cures for these skin cancers, even though it penetrated deeper than the tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up and histological changes of superficial nonmelanoma skin cancers treated with topical delta-aminolevulinic acid photodynamic therapy. Fink-Puches, R., Soyer, HP., Hofer, A., et al.[2022]

Photodynamic therapy (PDT) using 20% methyl aminolevulinate cream showed high clearance rates of 89% for low-risk and 87% for high-risk nodular basal cell carcinoma (BCC) after 30 days, indicating its efficacy in treating this type of skin cancer.

The recurrence-free survival rates at 60 months were also comparable, with 82% for high-risk and 85% for low-risk areas, suggesting that PDT is a viable treatment option for nodular BCC less than 5 mm, even in high-risk locations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy for nodular basal cell carcinoma up to 5 mm located on high-risk area: effectiveness and long-term follow-up results. Salvio, AG., Requena, MB., Stringasci, MD., et al.[2023]

In a pilot study involving 24 patients with 112 superficial basal cell carcinomas (BCC), both 10% ALA and methyl-ALA (mALA) thermogels showed a 60% success rate in treating tumors after the first session.

Despite the expectation that mALA would provide better penetration and therapeutic outcomes, the results indicated no significant difference in efficacy between mALA and ALA treatments, suggesting further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of aminolevulinic acid (ALA)-thermogel-PDT with methyl-ALA-thermogel-PDT in basal cell carcinoma. Schleier, P., Berndt, A., Kolossa, S., et al.[2022]

In a clinical study involving 19 patients with 55 superficial basal cell carcinomas, 85% of the tumors showed a complete response to photodynamic therapy using a novel nanocolloid lotion of 5-aminolevulinic acid (5-ALA) after just one treatment.

The treatment was well tolerated without the need for local anesthetics, causing only slight discomfort during the light irradiation, indicating its safety and convenience for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy of superficial basal cell carcinomas using topical 5-aminolevulinic acid in a nanocolloid lotion. Hürlimann, AF., Hänggi, G., Panizzon, RG.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3726902/

Aminolevulinic Acid-Photodynamic Therapy of Basal Cell ... This study was designed with the aim of evaluating the efficacy of PDT in treatment of BCC and factors that may affect the response rate. Materials and Methods:.

2. sciencedirect.com sciencedirect.com/science/article/pii/S157210002500239X

Efficacy and aesthetic outcomes of photodynamic therapy ... ALA-PDT achieves precise tumor eradication while preserving critical facial anatomy, serving as a viable first-line option for anatomically complex BCCs in ...

3. jaad.org jaad.org/article/S0190-9622(25)02656-8/fulltext

Red light photodynamic therapy with 10% aminolevulinic ... Red light photodynamic therapy with 10% aminolevulinic acid gel showed efficacy for treatment of superficial basal cell carcinoma in a ...

4. onclive.com onclive.com/view/phase-3-study-of-ameluz-pdt-in-superficial-basal-cell-carcinoma-reaches-1-year-follow-up-to-support-fda-snda-submission

Phase 3 Study of Ameluz-PDT in Superficial Basal Cell ... The ALA-BCC-CT013 study showed significant efficacy of Ameluz/PDT in treating sBCC, achieving high clinical and histological clearance rates.

5. frontiersin.org frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1089361/full

Photodynamic therapy for skin carcinomas: A systematic ... The aim of this study was to determine the relative efficacy and safety of PDT compared with placebo or other interventions for the treatment of skin ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1572100025001814

5-aminolevulinic acid photodynamic therapy for the ... 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is used off-label in the US to treat basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Bowen ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11136039/

Photodynamic Therapy for the Treatment of Basal Cell ... PDT is a safe and efficacious treatment option for sBCC and to a lesser extent nBCC. Keywords: basal cell carcinoma, photodynamic therapy, 5-aminolevulinic acid ...

8. medicalpolicy.bcbstx.com medicalpolicy.bcbstx.com/content/dam/bcbs/medicalpolicy/pdf/therapy/THE801.027_2024-12-15.pdf

Dermatologic Applications of Photodynamic Therapy (PDT) The authors reported that the follow-up phase data confirmed the efficacy and safety of PDT with BF-200 ALA. No p-values or CIs were reported.