Photodynamic Therapy for Lentigo Maligna Using 5-aminolevulinic Acid Nanoemulsion as a Light Sensitizing Cream (LM PDT)

Photodynamic Therapy for Melanoma Precursor Lesion Lentigo Maligna Using 5-aminolevulinic Acid Nanoemulsion (BF-200 ALA) as a Light Sensitizing Cream

This study investigates the efficacy of photodynamic therapy (PDT) in the treatment of lentigo maligna (LM). Hyperspectral imaging system (HIS) will be used to determine the margins of LM and to rule out possible invasion. Participants will receive photodynamic therapy three times consecutively with intervals of two weeks using 5-aminolevulinic acid nanoemulsion (BF-200 ALA, Ameluz®) as a light sensitizing cream. Four weeks after last photodynamic therapy the lentigo maligna lesion will be excised surgically from the skin. Result of the treatment is assessed with histopathological examination and immunohistochemical staining of removed tissue specimen.

Study Overview

• Status: Completed
• Conditions: Lentigo Maligna
• Intervention / Treatment: Drug: 5-aminolevulinic acid nanoemulsion

Detailed Description

Lentigo maligna (LM) is an in-situ form of melanoma which occurs on sun-exposed skin. Untreated LM can progress into invasive lentigo maligna melanoma (LMM). The incidence of LM/LMM is constantly increasing as the population grows older and lifelong sun-exposure is on the rise. Clinically it is difficult both to determine the borderline of LM as well as to differentiate LMM from LM. A novel imaging method hyperspectral imaging system (HIS) can be used for delineating margins of LM and for spotting invasion inside LM lesion. The gold standard treatment for LM is surgical excision with adequate (≥5 mm) margins. Due to large size of LM lesions and typical location on face or neck the surgical treatment is challenging and can cause aesthetic and functional deficit for the patient. Furthermore, LM patients tend to be elderly who may have anesthetic contraindications. Other treatment modalities for LM have been studied but none of them still has proved to be efficient enough. Recently, photodynamic treatment (PDT) has been suggested as a promising novel treatment method for LM.

In this prospective pilot study we investigate whether the photodynamic therapy (PDT) is effective for treatment of lentigo maligna. 10-15 patients with a histologically confirmed lentigo maligna are included in the trial. The study course is as follows: During the first visit in the clinic, the suspected LM lesion is examined clinically under Wood's lamp and imaged with a HIS camera. Elicited margins from both methods are marked on a transparent sheet and the treatment area is photographed. A biopsy is taken from the darkest-colored part of LM to confirm diagnosis and to rule out invasion. Next, the patients receive PDT treatment three times with 2 weeks' intervals. Before applying the Ameluz® light sensitizer gel the skin of treatment area is prepared with fractional ablative CO2-laser to enhance absorption. After light sensitizer absorption the LM lesion is illuminated with artificial red light (Aktilite CL128 lamp) using a light dose of 90 J/cm2. Finally 4 weeks after the last PDT treatment LM is excised surgically using 5 mm margins. The efficacy of PDT is assessed after surgical excision with histopathological examination and immunohistochemical staining (MART, Mel-5 and MITF stains). The final result of the treatment is controlled 6 months after the surgical excision.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• Finland
  • Lahti, Finland
    • Päijät-Häme Central hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with non-invasive lentigo maligna located in the skin of face, neck or upper body region

Exclusion Criteria:

• Biopsy shows invasive melanoma inside lentigo maligna lesion prior treatment
• Porphyria or solar dermatitis
• Allergy for photosensitizer (5-aminolaevulinic acid) used in study
• Pregnant or breastfeeding patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lentigo maligna patients; All the participants with histologically confirmed lentigo maligna will receive photodynamic therapy three times with 2 weeks' intervals. The borderline of treatment area is delineated with Wood's lamp and hyperspectral imaging system using 5 millimeter margins. Before applying the 5-aminolevulinic acid nanoemulsion (BF-200 ALA, Ameluz®) light sensitizing gel the skin of treatment area is prepared with fractional ablative CO2-laser to enhance absorption. Ameluz® is spread as a 1 millimeter thick layer on the skin. After light sensitizer absorption the treatment area is illuminated with artificial red light (Aktilite CL128 lamp) using a light dose of 90 J/cm2. Finally 4 weeks after the last PDT treatment LM is excised surgically using 5 mm margins.

Drug: 5-aminolevulinic acid nanoemulsion; A 1 millimeter thick layer of 5-aminolevulinic acid nanoemulsion light sensitizing gel is applied on the skin and let to absorb 3 hours before illumination.; Other Names: BF-200 ALA; Ameluz®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The histopathological and immunohistochemical curing of lentigo maligna	The efficacy of PDT treatment is assessed after surgical excision with histopathologic examination and immunohistochemical staining (MART, Mel-5 and MITF stains). The final result of the treatment is controlled 6 months after the surgical excision.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The changes in hyperspectral images induced by photodynamic therapy	The lentigo maligna will be imaged with hyperspectral imaging system before and after PDT treatment. The difference in hyperspectral images will be assessed.	2 months
The occurrence of TERT-mutations in Lentigo maligna	The participants' will be asked a separate permission to partake in a TERT (telomerase reverse transcriptase) gene study. If permission is granted a partial tissue specimen of excised lentigo maligna lesion will be sent to Heidelberg, Germany for analysis of TERT (telomerase reverse transcriptase) gene mutations.	2 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The experienced pain of participants during photodynamic therapy	Participants will be asked to fill visual analogue scales (VAS) of pain experienced during illumination phase of photodynamic therapy.	1 day
Delayed skin reactions after photodynamic therapy	The participants will have a nurse's appointment two days after the first PDT treatment to photograph and to evaluate the degree of delayed inflammatory skin reactions due to treatment. The skin reactions are also evaluated by the dermatologist during second and third PDT treatment.	2 days, 2 weeks

Collaborators and Investigators

• Sponsor: Joint Authority for Päijät-Häme Social and Health Care
• Collaborators: Tampere University; Huslab, Finland
• Investigators: Principal Investigator: Janne Räsänen, Lic. Med., Päijät-Häme Central hospital; Study Director: Mari Grönroos, D. Med. Sc., Päijät-Häme Central hospital; Study Chair: Noora Neittaanmäki-Perttu, D. Med. Sc., HUSLAB; Study Chair: Mari Salmivuori, Lic. Med., Päijät-Häme Central hospital; Study Chair: Leila Jeskanen, Lic. Med., HUSLAB; Study Chair: Erna Snellman, Professor, Tampere University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: February 13, 2016
• First Submitted That Met QC Criteria: February 13, 2016
• First Posted (Estimate): February 19, 2016

Study Record Updates

• Last Update Posted (Actual): May 30, 2018
• Last Update Submitted That Met QC Criteria: May 27, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Photodynamic Therapy; Hyperspectral Imaging; Lentigo Maligna
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Hyperpigmentation; Pigmentation Disorders; Melanosis; Melanoma; Lentigo; Hutchinson's Melanotic Freckle; Photosensitizing Agents; Dermatologic Agents; Aminolevulinic Acid
• Other Study ID Numbers: Q291dnro62/2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No