Imiquimod Versus Photodynamic Therapy of Actinic Keratoses in Organ Transplant Recipients

Study Overview
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Brief Summary
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The purpose of this study is to compare two different therapies for actinic keratoses in organ transplant recipients with regard to efficacy and tolerability. The investiagtors are planning to examine treatment with Imiquimod 5% cream versus treatment with Methyl-aminolaevulinate 16% cream and subsequent irradiation with red light, so-called photodynamic therapy, in this patients' group. A secondary objective of our study is to investigate the reduction in the field cancerisation after both treatments using fluorescence diagnostic method and digital imaging.

Detailed Description
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Organ transplant patients (OTP) require lifelong immunosuppressive therapy and consequently are prone to develop skin tumors, i.e skin cancer is the most frequent malignancy in organ transplant recipients. OTP frequently develop extensive areas of actinic damage, epidermal dysplasia, wich accounts for increased risk of aggressive skin cancer development in susceptible patients, and are referred to as field cancerisation. Therefore the whole area of field cancerisation has to be treated. In our study we will treat this areas with two different methods and not only the single visible lesions of actinic keratoses.In this open prospective randomized intraindividual study one half of the patients' scalp or face will be treated with Imiquimod 5% cream for 4 weeks, 3 times a week, and the other half with Methyl-aminolaevulinate 16% cream photodynamic therapy, two applications in two weeks interval. The pre- and post treatment extension of field cancerisation will be assessed by means of a highly sensitive digital fluorescence imaging system.

Official Title
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Topical Imiquimod 5% Cream Therapy Versus Photodynamic Therapy With Methyl-aminolaevulinate 16% Cream of Actinic Keratoses in Organ Transplant Recipients

Conditions
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Actinic Keratoses

Intervention / Treatment
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* Other: photodynamic therapy
* Drug: imiquimod 5% cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Patients who had received a kidney, liver, lung or heart transplant more than 3 years prior to inclusion into the study Patients who had been treated at least 6 months prior to study entry with a stable twofold or threefold immunosuppressive treatment Patients who had clinically confirmed epithelial dysplasia (actinic keratoses) in at least two anatomically separated contralateral areas on the face and/or scalp with comparable size and extension and minimum distance of 5 cm Exclusion Criteria: Invasive squamous cell carcinoma or basal cell carcinoma in the treatment area Known allergy to imiquimod and/or methyl-aminolaevulinate and/or one of the other components of the investigational products and/or peanut oil Patients who have received retinoids, interferons or investigational drugs within 4 weeks of study initiation Patients who are participating in othe dermatological study Persistent Hepatitis B or C infections Any evidence of systemic cancer Patients who have received any systemic cancer chemotherapy or radiation therapy Pregnant or lactating women Patients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: photodynamic therapy<br>Methyl-aminolaevulinate 16% cream (Metvix 160mg/g cream) will be applied 1 mm thick on the treated area, which has a maximal diameter of 8 cm2, and will be covered with a semipermeable dressing (Suprasorb F, Lohmann & Rauscher, Vienna, Austria)for 3 hours. Afterwards the cream leftovers will be removed by 0.9% NaCl solution. Following the treated area will be irradiated with heat-free visible red light at a peak wavelength of 630 nm with a single dose of 37 J/cm2 (Actilite model: CL128, PhotoCure, Norway). This treatment will be repeated in two weeks. | Other: photodynamic therapy<br>* Methyl-aminolaevulinate 16% cream (Metvix) will be applied on the treated area under occlusion for 3 hours. It follows irradiation with visible red light at a peak wavelength of 630 nm (Actilite CL128) with a single dose of 37 J/cm2.<br>* Other names: Metvix 160mg/g cream photodynamic therapy;|
| Active Comparator: imiquimod 5% cream<br>250 mg imiquimod 5% cream (Aldara 5% cream) will be applied over night, for a total of 3 nights in a week, for duration of 4 weeks. | Drug: imiquimod 5% cream<br>* 250 mg imiquimod 5% cream will be applied over night for a total of 3 nights in the week, for duration of 4 weeks<br>* Other names: Aldara 5% cream;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical complete response rate of actinic keratoses | The clinical complete response rate of actinic keratoses is defined as a proportion of the number of actinic keratoses with a clinically determined complete clearance(no visible and/or palpable actinic keratoses) to the number of the actinic keratoses at baseline. | 4 weeks after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical complete response rate of actinic keratoses | The clinical complete response rate of actinic keratoses is defined as a proportion of the number of actinic keratoses with a clinically determined complete clearance(no visible and/or palpable actinic keratoses) to the number of the actinic keratoses at baseline. | 6 and 12 months after end of treatment | 
| global reduction in the area of specific fluorescence | Prior to photodynamic therapy an illumination of the treated area with a Wood light will be prepared (fluorescence diagnostik). The specific fluorescence will be detected and documented using the non-invasive fluorescence-imaging system Dyaderm, Biocam, Germany. | 1, 6 and 12 months after end of treatment | 
| global patient's satisfaction | The global patient's satisfaction will be determined by the patients themselves on a 10 cm visual analog scale. 0 means extremely unsatisfied, 1-3 means unsatisfied, 5-7 means moderately satisfied, 8-10 means highly satisfied. | 3, 6 and 12 months after end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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actinic keratoses, organ transplant recipients, photodynamic therapy, imiquimod