Topical Vitamin D3, Diclofenac or a Combination of Both to Treat Basal Cell Carcinoma

Study Overview
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Brief Summary
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Basal cell carcinoma (BCC) is the most frequent malignant tumor in Caucasians and the incidence is still increasing with 3-8% each year. Since BCCs generally occur on sun-exposed areas of the skin, the rice in incidence is mainly explained by the increasing exposure to (intermittent) ultraviolet radiation. Surgical excision is still the standard treatment for (micro)nodular BCCs. The costs as well as the increased workload are stressing the health care system even further and posing BCC an important health care problem. Since half of the BCCs arise primarily on the face & (bald) head and treatment by surgical excision may result in disfiguring scars, patients often experience a dramatic decrease of their quality of life. Hence, there is an urgent medical and societal need for a simple and cheap (targeted) treatment, preferably to be performed by the patients themselves. This treatment must be safe and effective. Such treatment is not available yet. BCC tumorigenesis is complex and must be multifactorial. Genetic alterations of multiple components of the Sonic Hedgehog (SHH) pathway are involved in sporadic BCC pathogenesis; inactivating mutations in Patched-1 (PTCH1) and activating mutations of Smoothened (SMO) and Suppressor of Fused (SU(FU)). With this knowledge, inhibition of the SHH pathway by SMO antagonists was successfully administered, however treatment resulted only in partial clinical response ofBCC. Recently, involvement of the Wingless (Wnt) pathway has been proven to be essential in BCC tumorigenic response. Moreover, a recent study of our own department provides the first evidence that epigenetic alterations, particularly promoter hypermethylation, influence both the SHH and Wnt pathway (own data, not published), which can serve as therapeutic targets. Both non-steroidal anti-inflammatory drugs (NSAlDS) and vitamin D derivatives are able to directly or indirectly target the Wnt pathway. Furthermore, vitamin D3 is able to inhibit Smoothened (SMO) in vitro, resulting in inhibition of the SHH pathway. Although in vivo studies are lacking, the investigators assume that topical application of these drugs may inhibit BCC growth and/or may cure BCC and thus might provide very promising future perspectives. Calcitriol and NSAlDs ointments are both already available for other indications and save in use. Eventually, our approach may result in a systematic approach to BCC, targeting (epi)genetic changes to treat and/or prevent further tumour growth.

Official Title
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Topical Vitamin D3, Diclofenac or a Combination of Both to Treat Basal Cell Carcinoma

Conditions
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Basal Cell Carcinoma

Intervention / Treatment
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* Drug: Diclofenac
* Drug: Diclofenac + Calcitriol
* Drug: Calcitriol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Minimum age 18 years Primary basal cell carcinoma, histologically confirmed (Micro) Nodular or superficial histological subtype Comorbidities may not interfere with study treatment Capable to understand instructions Exclusion Criteria: Age under 18 years Tumors located at the H-zone of the face Deficient histological conformation Proven or suspected malignancy of other organs Not capable of comprehending instructions Incompetent Use of oral NSAlDs during the trial period or within 30 days before starting therapy Use of oral vitamin D (containing) supplements during the trial period or within 30 days before starting therapy

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: Solaraze<br> | Drug: Diclofenac<br>* Application on the lesion 2 times a day 8 weeks.<br>* Other names: Solaraze;|
| Active Comparator: Solaraze + Silkis<br> | Drug: Diclofenac + Calcitriol<br>* Application on the lesion 2 times a day, both ointments, 8 weeks.<br>* Other names: Solaraze + Silkis;|
| Active Comparator: Silkis<br> | Drug: Calcitriol<br>* Application on the lesion, 2 times a day, 8 weeks.<br>* Other names: Silkis;|
| No Intervention: No treatment<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological changes in different proliferation and apoptosis markers. | To determine the change in mean percentage of cells expressing Ki67 and BCL2 after topical application of Calcitriol (Silkis) 3 μg/g, Diclofenac 3% or a combination of both. | At baseline and after 8 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Macroscopic tumour changes | We want the observe if the tumour will also macroscopically change within 8 weeks of treatment. Things were we will focus on will be size and colour. | Baseline and after 8 weeks. | 
| Toleration | We want to evaluate if the patients will tolerate the therapy. Main points in here will be irritation of the skin and the amount of time this therapy costs the patients. | 8 weeks | 
| Compliance | Data for compliance with the prescribed regimens of either diclofenac sodium-3% gel, calcitriol 3µg/g ointment or a combination of both will be obtained from a personal diary kept by patients and completed once a week during treatment. Compliance was calculated as the number of applications done by the patient divided by the total prescribed number of applications. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Topical, Diclofenac, Vitamin D3