Actinic Keratosis Study

Study Overview
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Brief Summary
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The main purpose of this study is to determine the effectiveness of a new combination therapy for actinic keratosis. This study investigates a new indication for an FDA-approved topical medication, calcipotriol, for treatment of actinic keratosis, including how well it works and how safe it is when used in combination with the standard of care medication (5-fluorouracil) for the skin condition.

Official Title
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The Role of Calcipotriol in Treatment of Pre-cancerous Skin Lesions

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: 5-fluorouracil 5% cream
* Drug: Calcipotriol 0.005% ointment
* Drug: Vaseline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of at least 50 years Presence of four to fifteen clinically typical, visible, and discrete actinic keratoses in 25 cm2 on any of the four anatomical sites: scalp, face, right upper extremity and left upper extremity Ability and willingness of the patient to participate in the study (Informed consent is obtained) Exclusion Criteria: Treatment area is within 5 cm of an incompletely healed wound or a suspected basal-cell or squamous-cell carcinoma Treatment area contained hypertrophic and hyperkeratotic lesions, cutaneous horns, or lesions that had not responded to repeated cryotherapy Recent (within a month) use of medications that could interfere with evaluation of the treatment area (e.g., topical medications, artificial tanners, immunosuppressive medications, immunomodulating agents, cytotoxic drugs, ultraviolet B phototherapy, other therapies for actinic keratoses, or oral retinoids) Premenopausal Women (to avoid any risk of pregnancy) History of hypercalcemia or clinical evidence of vitamin D toxicity

Ages Eligible for Study
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Minimum Age: 50 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: calcipotriol plus 5-fluorouracil<br>calcipotriol 0.005% ointment and 5-fluorouracil 5% cream are mixed at 1:1 weight ratio. The compounded medication is applied topically twice a day for 4 days. | Drug: 5-fluorouracil 5% cream<br> <br> * Other names: Efudex;Drug: Calcipotriol 0.005% ointment<br> <br> * Other names: MC 903;|
| Active Comparator: 5-fluorouracil plus vaseline<br>5-fluorouracil 5% cream and vaseline are mixed at 1:1 weight ratio. The compounded medication is applied topically twice a day for 4 days. | Drug: 5-fluorouracil 5% cream<br> <br> * Other names: Efudex;Drug: Vaseline<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of change in the number of actinic keratoses from baseline | To compare the efficacy of topical 5-fluorouracil+calcipotriol vs. 5-fluorouracil alone in treatment of actinic keratosis in patients with multiple actinic keratoses at each of the four anatomical sites (scalp, face, right upper extremity and left upper extremity). The outcome of interest is percentage change from baseline number of actinic keratoses in the target treatment area on scalp, face, right upper extremity and left upper extremity at 8 weeks after treatment. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete and partial (>75%) clearance of actinic keratoses | o To determine complete and partial (>75%) clearance of actinic keratoses at 8 weeks after treatment. | 8wks | 
| Composite score of erythema, itching and skin pain after topical 5-fluorouracil+calcipotriol vs. 5-fluorouracil alone treatment of actinic keratoses | To determine the composite scores of erythema, itching and pain (determined using standardized scales) following topical application of 5-fluorouracil+calcipotriol vs. 5-fluorouracil alone at the end of the 4-day treatment period. | 4days | 
| Induction of TSLP expression in keratinocytes by calcipotriol | To examine the induction of TSLP expression in keratinocytes by calcipotriol at the site of the actinic keratoses at the end of 4-day treatment of course. | 4 days | 
| differences in response to topical 5-fluorouracil+calcipotriol vs. 5-fluorouracil alone between the four anatomical sites | To determine any differences in response to topical 5-fluorouracil+calcipotriol vs. 5-fluorouracil alone between the four anatomical sites at 8 weeks after treatment. | 8wks |