Spots Global Cancer Trial Database for Effects of Topical Diclofenac on Tumor Metabolism

Study Description

Brief Summary: The rationale of this study is to investigate the effects of topical diclofenac on tumor metabolism in the treatment of actinic keratoses in immunocompetent and immunocompromised patients. Study hypothesis is that topical diclofenac lowers lactate level in skin biopsies of actinic keratoses. Planned number of patients is 38. This study is a monocenter study investigating the effects of 3% diclofenac in 2.5% hyaluronic acid gel on tumor metabolism in the treatment of actinic keratoses. Treatment duration is 3 months. Skin biopsies will be obtained before treatment, at the end of the treatment and four weeks after the treatment. Control biopsies at visit 1 and 3 are performed in healthy, sun damaged and untreated skin. Evaluation of efficacy will be performed at the end of the treatment and four weeks after the treatment. Duration of treatment is 3 months (±4 weeks). Approximately 0,5g Solaraze® 3% gel is applied on a 5cm x 5cm lesion. Solaraze® 3% gel is applied twice daily on the study lesions.

Detailed Description: Neoplastic cells show an increased glucose metabolism and glycolysis which is associated with high lactate concentrations. There is also data for several tumor entities that high levels of lactate in the tumor are associated with tumor progression, metastasis and poor clinical outcome. Kreutz et al. demonstrated that diclofenac inhibits tumor cell proliferation in vitro and tumor growth in vivo via COX-independent effects on glucose metabolism. Diclofenac is taken up by tumor cells and inhibits tumor cell proliferation through inhibition of the oncogene MYC and subsequently glycolysis and block of lactate transport. MYC regulates genes involved in glycolysis and is upregulated in neoplastic cells, which is in line with the metabolic switch to glycolysis, the so called "Warburg effect", that cancer cells show. Although these results were found in vitro using human melanoma cells and in vivo in a mouse model, a similar mechanism of action is assumed to be relevant for the treatment of actinic keratoses with topical diclofenac. However tumor metabolism in diclofenac-treated actinic keratoses has never been investigated. To investigate the mechanism of action of diclofenac in the treatment of actinic keratoses, a clinical study analyzing particularly lactate levels, glycolysis and inflammatory infiltrate is needed.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

Useful links and downloads for this trial