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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the treatment ALA, Aminolevulinic Acid, Levulan, Ameluz for basal cell carcinoma?

Research shows that photodynamic therapy (PDT) using aminolevulinic acid (ALA) is effective for treating superficial basal cell carcinoma, offering benefits like minimal scarring and good cosmetic results. It is also noted for its ability to treat multiple skin lesions at once. ^{1 2 3 4 5}

Is photodynamic therapy (PDT) using aminolevulinic acid (ALA) safe for treating basal cell carcinoma?

Research indicates that photodynamic therapy (PDT) using aminolevulinic acid (ALA) is generally safe for treating superficial basal cell carcinoma, with studies showing good safety profiles and minimal side effects. ^{1 3 5 6 7}

How is the treatment ALA-PDT unique for basal cell carcinoma?

ALA-PDT (Aminolevulinic Acid Photodynamic Therapy) is unique because it is a noninvasive treatment that uses light to activate a drug applied to the skin, leading to excellent cosmetic results with little to no scarring. It can treat multiple lesions at once and is particularly effective for superficial basal cell carcinoma, unlike some traditional treatments. ^{1 5 6 8 9}

Research Team

Edward Maytin, MD, PhD

Principal Investigator

Cleveland Clinic, Case Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

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 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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Photodynamic therapy of superficial basal cell carcinomas using topical 5-aminolevulinic acid in a nanocolloid lotion. [2018]

2. United States 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. [2022]

3. Netherlands 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Photodynamic therapy using methyl aminolevulinate acid in eyelid basal cell carcinoma: a 5-year follow-up study. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Aminolevulinic acid photodynamic therapy for skin cancers. [2013]

6. England 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. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Photodynamic therapy with 5-aminolevulinate patch for the treatment of superficial basal cell carcinomas. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of aminolevulinic acid (ALA)-thermogel-PDT with methyl-ALA-thermogel-PDT in basal cell carcinoma. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Photodynamic therapy of cutaneous lymphoma using 5-aminolevulinic acid topical application. [2019]