Actinic Keratoses (gr I-III) Clinical Trial
— 2013-002108-15Official title:
Treating Actinic Keratoses With Natural Daylight PDT: Comparing Two Light Sensitizers (ALA and MAL)
Actinic keratoses (AKs) are superficial premalignant skin lesions that can progress into an
invasive or metasthatic squamous cell carcinoma. AKs can be treated with photodynamic
therapy (PDT), of which cure rate compares to cryo surgery with an excellent cosmesis. In
PDT the AK lesions are first curettaged, then a photosensitizer is applied on the skin and
let to absorb for 3 hours. The skin is illuminated using a blue or red light source light
source depending on the sensitizer, which induces activation of protoporphyrin IX (PpIX) and
phototoxic reaction destroying the cancer cells.
The approved photosensitizers in Europe are methylaminolevulenic acid cream, (MAL, Metvix™,
Galderma), a patch containing 5-aminolevulenic acid (5-ALA, Alacare®, Spirig AG) and
aminolevulenic acid gel (BF-200 ALA, Ameluz®, Biofrontera AG) to be used with a red LED
light (630-635 nm). In North America a 5-aminolevulinic acid stick (5-ALA, Levulan®
Kerastick) can also be used with a blue light source (417 nm).
PpIX absorption peaks are within the visual spectrum of light, which allows PpIX daylight
activation. During natural daylight PDT (NDL-PDT) protocol, PpIX is continuously activated
during its development, whereas in conventional PDT (LED-PDT) using red LED lamps, large
amounts of accumulated PpIX are momentarily activated.
Since skin field cancerization refers to presence of different degrees of visible and
invisible dysplastic changes, the whole area should be treated to prevent the development of
non-melanoma skin cancers (NMSCs). NDL-PDT enables treatment of field cancerization in one
sitting whereas LED-PDT may need repeated illuminations to cover the whole area. NDL-PDT
results in enhanced cost-efficacy due to reduced staff expenses, since there's no need for
policlinical sensitizer absorption and illumination.
At the moment two photosensitizers have marketing authorization in Finland, ALA (Ameluz®)
and MAL (Metvix™). Ameluz® holds a lower unit price and it's clearance rate compares to
Metvix™ in LED-PDT. We are piloting a study comparing the cost-efficacy of these two light
sensitizers in NDL-PDT. Our hypothesis is that there will be at least 0,30 difference in the
histopathological curing of the lesions. Our other hypothesis is that Ameluz® with it's
lower unit price results in reduced treatment costs and better cost-efficacy compared to
Metvix™. The efficacy of the treatments will be assessed clinically, histopathologically,
immunohistochemically and by hyper spectrum camera imaging.
| Status | Completed |
| Enrollment | 20 |
| Est. completion date | December 2014 |
| Est. primary completion date | December 2014 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - actinic keratoses on boths sides of the face or scalp - age over 18 years - there must be atleast one ak of over 6mm on both sides - patients must be able to make the decision to attend independently Exclusion Criteria: - pregnancy - lactation - lack of compliance |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Finland | Päijät-Häme Central Hospital | Lahti |
| Lead Sponsor | Collaborator |
|---|---|
| Joint Authority for Päijät-Häme Social and Health Care |
Finland,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Primary treatment reaction | The primary treatment reaction will be single-blindedly assessed one week after the treatment. A dermatologist will assess which side of the face or scalp presents a stronger reaction. | 1 week | Yes |
| Other | Dermatoecological analyses of the treatment costs | Researchers will analyze the cost-efficacy of the treatments using decision tree, sensitivity analysis, ICER and QALY-analyses to decide with treatment modality is more preferrable. The differences in cost-efficacy will most likely depend on the light sensitizer costs and their efficacy on the treated lesions. | 3 months | No |
| Other | Hyper spectrum imaging | Hyper spectrum camera images will be taken before treatment and 3 months after the treatment to assess the healing of field cancerization and actinic keratoses areas. | 3 months | No |
| Primary | Histopathological healing of actinic keratoses | We will take 3mm punch biopsies of similar looking AKs from both sides of the face or scalp before the treatment and 3 months after the treatment to assess the histopathological healing of actinic keratoses. We will also make immunohistochemical analyses of P53 chromosome mutations from the taken biopsies. | 3 months | No |
| Secondary | Difference between pain experienced by the patient: comparing symmetrical areas of face or scalp | Patients will be asked to fill visual analogue scales about pain experienced by the patients on each sides of the face or scalp. Pain is assessed after the treatment until the evening. | 1 day | No |