Photodynamic Therapy Using Topical Aminolevulinic Acid in Treating Patients With Actinic Keratosis

Study Overview
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Brief Summary
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RATIONALE: Photodynamic therapy uses a drug that becomes active when it is exposed to a certain kind of light. When the drug is active, abnormal cells are killed. Photodynamic therapy using topical aminolevulinic acid may be effective against actinic keratosis. PURPOSE: This randomized clinical trial is studying how well different photodynamic therapy regimens using topical aminolevulinic acid work in treating patients with actinic keratosis.

Detailed Description
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OBJECTIVES: Primary To determine, using fluorescence measurements, the protoporphyrin IX (PpIX) accumulation in thin actinic keratoses (AK) and actinically damaged skin on the face, scalp, and upper torso (stratum 1) and the PpIX accumulation in thick AK and actinically damaged skin on the arms and legs (stratum 2) as a function of skin preparation, aminolevulinic acid (ALA) application time, and body site. To determine the extent that the PpIX is photobleached by the treatment light. Secondary To assess the effects of different treatment conditions on acute reactions of AK and sun damaged skin to ALA-photodynamic therapy (PDT) occurring 24-48 hours after PDT. To assess the effects of different treatment conditions on the efficacy of ALA-PDT. To examine the histological response to ALA-PDT. To determine, using fluorescence measurements, the PpIX accumulation in incidental thick AK that may occur in stratum 1, and the PpIX accumulation in incidental thin AK that may occur in stratum 2 as a function of skin preparation, ALA application time and body site. To determine the extent that the PpIX in these incidental lesions is photobleached by treatment light. OUTLINE: The randomization is a two-step restricted block process for application time and skin preparation, followed by randomization for light dose (1 vs 2 pulses) within the anatomic site. Within each stratum (stratum 1 or 2), lesions in each separate anatomic area (face and neck, scalp, upper torso; arms, legs) are randomized to receive 1 of 3 pretreatment skin preparation before receiving topical aminolevulinic acid (ALA): pretreatment with acetone, gentle abrading, or no pretreatment. Patients are randomized to receive ALA at different times before the photodynamic therapy (PDT). Arm I: Patients receive topical ALA 2 hours before PDT. Arm II: Patients receive topical ALA 4 hours before PDT. Arm III: Patients receive topical ALA 24 hours before PDT. Each anatomic area is divided into subunits (e.g., right and left arm, right and left side of the face). The subunits are randomized to receive 1 or 2 pulses of the laser treatment. Arm IV: 1 Vbeam laser pulse (photodynamic therapy) is applied to the subunit. Arm V: 2 Vbeam laser pulses (photodynamic therapy) are applied to the subunit. Patients may receive up to 3 treatments (including pretreatment, ALA, and PDT) at least 1 month apart. Patients with progressive lesions or lesions that have not responded after 3 treatments may receive diagnostic biopsy to check for invasive squamous cell carcinoma and referred to treatment off study. Patients undergo biopsies at baseline, before and after ALA application prior to light treatment, and up to 24 hours after light treatment to analyze cytokines and genes specific to actinic keratoses.

Official Title
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A Pilot Study to Investigate the Use of Topical Levulan® With Vbeam® Laser for the Treatment of Actinic Keratoses

Conditions
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Precancerous/Nonmalignant Condition

Intervention / Treatment
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* Drug: aminolevulinic acid
* Procedure: laser therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Actinic keratosis lesion located in any of the following body sites: Stratum 1*: face and neck, scalp, or upper torso At least 1 clinically evident thin actinic keratosis on each side of the midline of any of the above areas Stratum 2*: arms or legs At least 1 clinically evident thick actinic keratosis on each arm or leg NOTE: *One patient may be in one or both strata depending on the location of the lesion(s) Lesions to be treated on this protocol must not have been previously treated by other modalities for at least 2 months prior to study entry PATIENT CHARACTERISTICS: No porphyria or known hypersensitivity to porphyrins No known photosensitivity disease No known sensitivity to any components of aminolevulinic acid topical solution Not pregnant or nursing PRIOR CONCURRENT THERAPY: Other concurrent topical therapies at lesion sites other than those used in this protocol are allowed No other concurrent photosensitizer drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Arm 1 - ALA<br>Patients receive topical ALA topical (aminolevulinic acid) 2 hours before PDT. | Drug: aminolevulinic acid<br> <br> |
| Experimental: Arm 2<br>Patients receive topical ALA topical (aminolevulinic acid) 4 hours before PDT | Drug: aminolevulinic acid<br> <br> |
| Experimental: Arm 3<br>Patients receive topical ALA (aminolevulinic acid) 24 hours before PDT. Each anatomic area is divided into subunits (e.g., right and left arm, right and left side of the face). The subunits are randomized to receive 1 or 2 pulses of the laser treatment | Drug: aminolevulinic acid<br> <br> |
| Experimental: Arm 4<br>Vbeam laser pulse (photodynamic therapy) is applied to the subunit | Procedure: laser therapy<br> <br> |
| Experimental: Arm 5<br>Vbeam laser pulses (photodynamic therapy) are applied to the subunit. Patients may receive up to 3 treatments (including pretreatment, ALA, and PDT) at least 1 month apart | Procedure: laser therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Protoporphyrin IX (PpIX) Accumulation as a Function of Skin Preparation, Aminolevulinic Acid Application Time, and Body Site |  |  | 
| Extent That the PpIX is Photobleached by the Treatment Light |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of Different Treatment Conditions on Acute Reactions of Actinic Keratoses (AK) and Sun Damaged Skin Occurring 24-48 Hours After Photodynamic Therapy |  |  | 
| Effects of Different Treatment Conditions on Efficacy |  |  | 
| Histological Response |  |  | 
| PpIX Accumulation in Incidental AK as a Function of Skin Preparation, Aminolevulinic Acid Application Time, and Body Site |  |  | 
| Extent That the PpIX is Photobleached by the Treatment Light in Incidental Lesions |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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actinic keratosis