Laser Assisted Drug Delivery in the Treatment of Superficial Non Melanoma Skin Cancer: a Randomized Controlled Trial

Study Overview
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Brief Summary
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Photodynamic therapy (PDT) is a well established treatment option for superficial non melanoma skin cancer, such as superficial basal cell carcinoma (sBCC) and Bowen Disease (BD). However, a limited uptake of the topically applied photosensitizer methyl aminolevulinate (MAL) may reduce its efficacy. Pretreatment with an ablative carbon dioxide (CO2) laser has recently been studied in order to enhance the skin penetration of this photosensitizer. This study compares the results of a full ablative and a fractional ablative CO2 laser mode as pretreatment of PDT in the management of sBCC and BD. The endpoints efficacy, pain, aesthetics and patient preference are investigated during twelve months of follow up.

Detailed Description
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Superficial Basal Cell Carcinoma (sBCC) and Bowen Disease (BD) are malignant skin tumors localised in the superficial epidermis. These tumors are highly prevalent in the caucasian population. Diagnosis of sBCC and BD is often delayed because the clinical manifestation may be discrete and lesions are sometimes wrongly diagnosed and treated as eczema. Once the diagnosis is established, the lesions may cover an extensive area, making surgical excision more difficult. At that moment, the physician can make use of less invasive techniques such as photodynamic therapy (PDT). Pretreatment with an ablative carbon dioxide (CO2) laser has recently been studied in order to enhance the skin penetration of the photosensitizer methyl aminolevulinate (MAL). This study compares the results of a full ablative and a fractional ablative CO2 laser mode as pretreatment of PDT in the management of sBCC and BD. Ablation of the upper epiderm of the cancer results in an deeper penetration of MAL. Fractional ablation is known to result in better wound healing compared to full ablative CO2 laser ablation, because only small skin columns are ablated instead of the entire epidermal layer. Patients with non operable sBCC or BD lesions covering an area of at least 5 cm2 or with the presence of two small separated lesions, will be investigated. Lesions greater than 5 cm2 are divided in two. After randomization, the half of the lesions will be pretreated with the full ablative CO2 laser, while the other half with the fractional ablative CO2 laser. Afterwards, the entire surface is treated with MAL-PDT. Such as in our current clinical practice, this treatment modality is repeated after a two week interval. Thus, every subject undergoes both treatment modalities, making within-patient comparison possible. The endpoints efficacy, pain, aesthetics and patient preference are investigated during twelve months of follow up.

Official Title
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A Randomized Controlled Trial of a Full and a Fractional Ablative Carbon Dioxide Laser as Pretreatment for Photodynamic Therapy in the Management of Superficial Non Melanoma Skin Cancer

Conditions
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Bowen's Disease, Superficial Basal Cell Carcinoma

Intervention / Treatment
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* Device: full ablative CO2 laser
* Device: fractional ablative CO2 laser
* Drug: MAL
* Device: LED lamp
* Drug: lidocaine hydrochloride 2% with epinephrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with the presence of non operable superficial Basal Cell Carcinoma or Bowen's Disease lesions and the presence of at least two lesions or the presence of one lesion covering an area greater than 5cm2 Exclusion Criteria: pregnancy and/or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Full ablative CO2 laser + MAL PDT<br>The treatment starts with a full ablative CO2 laser pretreatment under local anaesthesia with injectable lidocaine hydrochloride 2% with epinephrine. This ablation is followed by photodynamic therapy: MAL is topically applied, followed by a 3 hours incubation under occlusion, whereafter 10 minutes of illumination with a LED lamp. This treatment is repeated after 14 days. | Device: full ablative CO2 laser<br>* ablation to the level of de dermal papilla<br>* Other names: full ablative carbon dioxide laser;Drug: MAL<br> <br> * Other names: Metvix® (Galderma);Device: LED lamp<br>* peak wavelength 630 nm, 37J/cm2<br>* Other names: light-emitting diodes;Drug: lidocaine hydrochloride 2% with epinephrine<br> <br> * Other names: xylocaine® 2% with epinephrine;|
| Active Comparator: Fractional ablative CO2 laser+ MAL PDT<br>The treatment starts with a fractional ablative CO2 laser ablation under local anaesthesia with injectable lidocaine hydrochloride 2% with epinephrine. This ablation is followed by photodynamic therapy: MAL is topically applied, followed by a 3 hours incubation under occlusion, whereafter 10 minutes of illumination with LED lamp. This treatment is repeated after 14 days. | Device: fractional ablative CO2 laser<br>* 180 micron HP, pulse 8ms, 15% overlay, 30 W (943J/cm)<br>* Other names: fractional ablative carbon dioxide laser;Drug: MAL<br> <br> * Other names: Metvix® (Galderma);Device: LED lamp<br>* peak wavelength 630 nm, 37J/cm2<br>* Other names: light-emitting diodes;Drug: lidocaine hydrochloride 2% with epinephrine<br> <br> * Other names: xylocaine® 2% with epinephrine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical efficacy after twelve months of follow up | A three point scale with complete regression (CR), partial regression (PR) and no regression (NR) defined respectively as 100%, 25-99% and 0-25% regression. | month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical efficacy after six months of follow up | A three point scale with complete regression (CR), partial regression (PR) and no regression (NR) defined respectively as 100%, 25-99% and 0-25% regression. | month 6 | 
| Clinical efficacy after three months of follow up | A three point scale with complete regression (CR), partial regression (PR) and no regression (NR) defined respectively as 100%, 25-99% and 0-25% regression. | month 3 | 
| Histological efficacy after twelve months of follow up |  | month 12 | 
| Pain during the first treatment session | The experienced pain during the treatment is scored bye the patient using a VAS scale of 100 mm. | immediately after the first treatment session (day 1) | 
| Pain during the second treatment session | The experienced pain during the treatment is scored by the patient using a VAS scale of 100 mm. | immediately after the second treatment session (day 14) | 
| Side effects after the first treatment session | The presence of following side effects is evaluated by the investigator: erythema, vesicles, pigment changes, scarring, infection and pain. | immediately after the first treatment session (day 1) | 
| Side effects after one week of follow up, telephone survey | The presence of following side effects is evaluated by the patient: erythema, vesicles, pigment changes, scarring, infection and pain. | day 7 | 
| Side effects before the second treatment session | The presence of following side effects is evaluated by the investigator: erythema, vesicles, pigment changes, scarring, infection and pain. | before initiation of the second treatment session (day 14) | 
| Side effects after the second treatment | The presence of following side effects is evaluated by the investigator: erythema, vesicles, pigment changes, scarring, infection and pain. | immediately after the second treatment session (day 14) | 
| Side effects after two weeks of follow up, telephone survey | The presence of following side effects is evaluated by the patient: erythema, vesicles, pigment changes, scarring, infection and pain. | day 21 | 
| Side effects after three months follow up | The presence of following side effects is evaluated by the investigator: erythema, vesicles, pigment changes, scarring, infection and pain. | month 3 | 
| Side effects after six months of follow up | The presence of following side effects is evaluated by the investigator: erythema, vesicles, pigment changes, scarring, infection and pain. | month 6 | 
| Side effects after twelve months of follow up | The presence of following side effects is evaluated by the investigator: erythema, vesicles, pigment changes, scarring, infection and pain. | month 12 | 
| Aesthetic result after three months of follow up | The aesthetic result is scored by a blinded investigator using a four point scale: excellent (no significant changes), good (minor changes), poor (serious dyspigmentation, visible scarring), very poor (important scarring). | month 3 | 
| Aesthetic result after six months of follow up | The aesthetic result is scored a by blinded investigator using a four point scale: excellent (no significant changes), good (minor changes), poor (serious dyspigmentation, visible scarring), very poor (important scarring). | month 6 | 
| Aesthetic result after twelve months of follow up | The aesthetic result is scored a by blinded investigator using a four point scale: excellent (no significant changes), good (minor changes), poor (serious dyspigmentation, visible scarring), very poor (important scarring). | month 12 | 
| Aesthetic result according to the patient after three months of follow up | The aesthetic result is scored by the patient using a four point scale: excellent (no significant changes), good (minor changes), poor (serious dyspigmentation, visible scarring), very poor (important scarring). | month 3 | 
| Aesthetic result according to the patient after six months of follow up | The aesthetic result is scored by the patient using a four point scale: excellent (no significant changes), good (minor changes), poor (serious dyspigmentation, visible scarring), very poor (important scarring). | month 6 | 
| Aesthetic result according to the patient after twelve months of follow up | The aesthetic result is scored by the patient using a four point scale: excellent (no significant changes), good (minor changes), poor (serious dyspigmentation, visible scarring), very poor (important scarring). | month 12 | 
| Technique of preference according to the patient | Patients are asked for their preferred therapy. Following options exist: (1) full ablative CO2 laser + PDT, (2) fractional ablative CO2 laser + PDT, (3) no preference | month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PDT, Bowen's Disease, Superficial Basal Cel Carcinoma, Non melanoma skin cancer, Photodynamic therapy, CO2 laser, Laser assisted drug delivery, Carbon dioxide laser, Laser assisted photodynamic therapy