Neoplasms

Symptoms and General Pathology

All Conditions

Mouth and Tooth Diseases

Rare Diseases

Leukoplakia

Cheilitis

Erythroplasia

Precancerous Conditions

Pathological Conditions, Anatomical

Mouth Diseases

Stomatognathic Diseases

Erythroplakia

Actinic Cheilitis

Dermatologic Agents

All Drugs and Chemicals

Aminolevulinic Acid

Photosensitizing Agents

Metil 5-aminolevulinate arm with photo activation.

Placebo (without metil 5-aminolevulinate) arm with photo activation.

Scrubbing lip vermillion and applying the medication or placebo that is activated (or not, in case of placebo) with red light.

Metil 5-aminolevulinate

Daniel Cohen Goldemberg, PhD

Brazil is a tropical country, with high incidence of ultraviolet radiation throughout the year. Many Europeans migrated to Brazil escaping either war or economic crisis to live in the country searching for opportunities. Low phototype combined with high incidence of UV light is a combination that not only affect the skin but also the lips. The current study was designed to use photodynamic therapy with metil 5-aminolevulinate for actinic cheilitis in a phase 2 clinical trial.

Photodynamic Therapy With Metil 5-aminolevulinate for Actinic Cheilitis - Phase 2 Clinical Trial

Photodynamic Therapy With Metil 5-aminolevulinate for Actinic Cheilitis - A Phase 2 Randomized Double-blind Placebo Controlled Clinical Trial

The Informed Consent Form (ICF) will be read and explained to each patient informing about all the risks and potential benefits. Clinical Study Report (CSR) is going to be registered for all patients, although data will not be shared.

Expected complete clinical response in 60% of cases

Expected histological cure in 40% of cases

Expression of immunohistochemical markers of cancer progression

Instituto Nacional de Cancer, Brazil

Photodynamic therapy with methyl aminolevulinate in the treatment of actinic cheilitis

Carcinoma

Carcinoma in Situ

Carcinoma, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Topical ALA will be applied to the entire lip surface and allowed to incubate for 60 minutes plus or minus 30 minutes. Blue light at a wavelength of 405-420 nm will be used for treatment at a dose of 1000 seconds.

Topical placebo will be applied to the entire lip surface and allowed to incubate for 60 minutes plus or minus 30 minutes. Blue light at a wavelength of 405-420 nm will be used for treatment at a dose of 1000 seconds.

Day 1: Screening and consent for this study. If eligible, a scouting biopsy will be obtained at 1 cm from the clinical border of the SCC for confirmation of AC.

7-14 Days after consultation: PDT to all subjects in the study. If during treatment a subject requests to discontinue due to pain the treatment will be terminated.

3-5 weeks after consultation: return for assessment. At this visit, the assigned treatment may be repeated if the treatment site is adequately healed. Re-treatment will only occur if there is persistent actinic damage.

6-8 weeks after consultation: Mohs surgery will be performed as per routine. Following tumor removal a scouting biopsy will be taken at a site 1 cm from the wound site created by SCC removal. The current waiting time for non-urgent surgery is 8 weeks. Standard care is not being altered for subjects in the study, other then their receiving the PDT intervention.

Photographs may be taken at each subject visit.

PDT prior to Mohs surgery

Gary Rogers, M.D.

Our study is designed to evaluate the efficacy of photodynamic therapy (PDT) for treatment of actinic cheilitis (AC) and as an adjunct to Mohs surgery for squamous cell carcinoma (SCC) on the lips. This study will utilize an FDA approved PDT modality (DUSA, Inc., Wilmington, MA 01887) using topical 5-amino-levulinic acid (ALA) for photosensitization followed by exposure to a Blu-U light source emitting 405-420nm wavelength light.

BACKGROUND:

SCC of the lip is commonly surrounded by extensive AC, which may affect part or all of the lip vermillion. While Mohs surgical technique with complete margin control is the preferred treatment for SCC at critical locations such as the lip, this technique is complicated by surrounding AC. AC and SCC in situ at the tumor edge make it difficult to achieve margins clear of dysplasia and as a result extra tissue beyond the invasive SCC often needs to be excised to ensure that the entire tumor is removed.

Non-surgical treatments when used alone to treat SCC give lower cure rates than surgical removal, and thus are not recommended as they place the subject at risk for recurrence and metastatic disease. Although one study reported high SCC clearance rates with PDT alone (24/25 SCCs histologically cleared), recurrence of 2 SCCs occurred and a metastasis to a LN was seen in one patient. (Kubler et al.)

Given that PDT has been shown to have significant efficacy for actinic keratoses and actinic cheilitis but is inadequate as primary treatment of lip SCC, we propose that PDT may be a useful adjunct to surgical resection, allowing for less extensive surgery after the dysplasia is addressed with PDT and potentially a lower recurrence rate. Although imiquimod and 5-FU are also used to treat cutaneous dysplasia, many favor PDT treatment due to its greater tolerability, shorter healing time, and more predictable host response.

There is significant data on the efficacy of PDT for treatment of actinic keratoses (AKs) and PDT is now FDA approved for treatment of AKs. (Piacquadio et al). Data on PDT for treatment of AC is much more limited, but small studies and case reports do indicate successful treatment of AC with regimens utilizing either topical 5-aminolevulinic acid (5-ALA), or a similar compound, methylaminopentanoate (MAL). The largest study with 5-ALA reports complete clinical clearance in 13/19 patients treated with 1 to 3 treatments of ALA plus Pulsed-dye laser (Alexiades). Sotiriou et al report that with two PDT treatments 8/10 patients had complete clinical and histologic clearance (Sotiriou). Case reports indicate similar success (Kodama; Stender). Efficacy has also been shown with MAL PDT. One study found that with two sessions of MAL + red light PDT complete histologic/ clinical clearance was seen in 7/15 cases of AC and partial clearance was seen in an additional 7/15 (Berking et al). Smaller studies and case reports have shown even higher response rates without clinical recurrence during short-term follow-up (Rossi et al; Hauschild et al). We have chosen 5-ALA plus blue light for PDT treatment in this study because it is FDA approved for treatment of AKs and ALA is available in the United States.

Specific Aims:

1. To determine whether pre-operative treatment of the lips with ALA PDT can reduce the size of post-surgical defects (scars) in subjects with AC and lip SCC
2. To determine whether ALA PDT applied to the lips can effectively clear actinic cheilitis (AC) and SCC in-situ (SCC-is) of the lip.
3. To assess the tolerability of ALA PDT for treatment of AC and SCC-is of the lips

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Photodynamic Therapy With Metil 5-aminolevulinate for Actinic Cheilitis - Phase 2 Clinical Trial	NCT03990636	Actinic Cheilit... Leukoplakia Erythroplakia	Metil 5-aminole...	18 Years -	Instituto Nacional de Cancer, Brazil
Photodynamic Therapy to Treat Actinic Damage in Patients With Squamous Cell Carcinoma (SCC) of the Lip	NCT00868088	Actinic Cheilit... Squamous Cell C... Squamous Cell C... Photodynamic Th... Mohs Surgery	PDT prior to Mo...	18 Years -	Tufts Medical Center
Photodynamic Therapy With Metil 5-aminolevulinate for Actinic Cheilitis - Phase 2 Clinical Trial	NCT03990636	Actinic Cheilit... Leukoplakia Erythroplakia	Metil 5-aminole...	18 Years -	Instituto Nacional de Cancer, Brazil

Spots Global Cancer Trial Database for actinic cheilitis