Treatment of Actinic Keratoses of the Face With Imiquimod 3.75% Cream Followed by Photodynamic Therapy

Study Overview
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Brief Summary
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The purpose of this study is to explore the effect of treating actinic keratoses of the face with imiquimod 3.75% cream followed by photodynamic therapy in comparison to treatment with imiquimod alone

Detailed Description
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Actinic keratoses are common skin lesions associated with solar ultraviolet radiation exposure. Some actinic keratoses may develop into skin cancers. Imiquimod 3.75% cream is an approved treatment for actinic keratoses that utilizes a regimen of application to the entire face or balding scalp of up to 2 packets of cream daily for two 2-week cycles, separated by a 2-week no treatment interval. Photodynamic therapy with aminolevulinic acid (ALA) 20% topical solution is also an approved treatment for actinic keratoses. ALA is applied to actinic keratoses, and after an incubation period, is excited with light. Although approved as a lesion-directed treatment for actinic keratoses, treatment of a field (e.g. face) with photodynamic therapy is commonly performed. Treatment with photodynamic therapy followed by imiquimod 5% cream has been reported in patients with actinic keratoses, basal cell carcinoma and Bowen's disease, and treatment with imiquimod 5% cream followed by photodynamic therapy in patients with vulvar intraepithelial neoplasia. There are, however, no prior studies on the safety and/or efficacy of using topical imiquimod 3.75% in conjunction with photodynamic therapy in the treatment of actinic keratoses. This study will use an open-label parallel cohort design in which all patients will received treatment with imiquimod 3.75% cream, and subsequently will be randomized to either photodynamic therapy or observation.

Official Title
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An Exploratory, Open-label Study of Sequential Field-directed Treatment of Actinic Keratoses of the Face With Imiquimod 3.75% Cream Followed by Photodynamic Therapy

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: Photodynamic therapy
* Drug: Imiquimod


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adults; 18 and over At least 10 and no more than 30 clinically typical actinic keratoses on the face Exclusion Criteria: Hypertrophic actinic keratoses or other skin lesions on the head that might required excluded treatment during the study Known contraindication to treatment with imiquimod or photodynamic therapy Condition that would limit compliance, be a potential safety risk, or require therapy with an excluded treatment Systemically immunocompromised Pregnant or nursing Dermatologic disease and/or condition in treatment area that might exacerbated by treatment with imiquimod, cause difficulty with examination, or require therapy with an excluded treatment Participation in another clinical study Treatment within the past 60 days with: Ultraviolet therapy Systemic immunomodulators Chemotherapeutic or cytotoxic agents Investigational agents Treatment on the head within the past 60 days with: Imiquimod Photodynamic therapy Red or blue light source therapy Cryotherapy or chemotherapy Surgical excision or curettage Topical corticosteroids Laser Dermabrasion Chemical peel Topical retinoids Topical 5-fluorouracil Topical pimecrolimus or tacrolimus Topical diclofenac Treatment for actinic keratoses on the head within the past 60 days

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imiquimod & photodynamic therapy<br>Imiquimod 3.75% applied to the entire face daily for 2 2-week cycles separated by a 2-week no treatment period, followed by one session of photodynamic therapy of the entire face with aminolevulinic acid and blue light | Drug: Photodynamic therapy<br>* Administered 4 weeks after completion of imiquimod therapy<br>* Other names: Levulan Kerasticks (aminolevulinic acid 20% solution);Drug: Imiquimod<br>* Imiquimod 3.75% cream, up to 2 packets, applied topically daily for two 2-week cycles separated by a no-treatment interval of 2-weeks, followed observation<br>* Other names: Zyclara (imiquimod 3.75% cream);|
| Active Comparator: Imiquimod<br>Imiquimod 3.75% applied to the entire face daily for 2 2-week cycles separated by a 2-week no treatment period, followed by observation | Drug: Imiquimod<br>* Imiquimod 3.75% cream, up to 2 packets, applied topically daily for two 2-week cycles separated by a no-treatment interval of 2-weeks, followed observation<br>* Other names: Zyclara (imiquimod 3.75% cream);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Actinic Keratosis Count | The percent change in actinic keratosis count as compared to the baseline lesion count | Week 18 (4 weeks after randomization visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Clearance | The proportion of randomized patients with complete clearance of actinic keratoses in the treatment area (entire face). | Week 18 (4 weeks after randomization visit) | 
| Cosmetic Appearance | Change (improvement) in investigator scores of cosmetic appearance of the treatment area (entire face) by objective and subjective assessments: INVESTIGATOR COSMETIC ASSESSMENT 0 - Facial skin is smooth to the touch, without significant lines or unevenness in pigmentation 1 - Facial skin shows 1 area (cheeks, forehead, or the perioral area) of significant 3 - Facial skin shows 3 areas with significant roughness, dyspigmentation, or fine lines 2 - Facial skin shows 2 areas of significant roughness, dyspigmentation, or fine lines 4 - All are severe in severity | Week 18 (4 weeks after randomization visit) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Imiquimod, Photodynamic therapy, Actinic keratoses, Sequential therapy, Therapeutic uses