Safety and Efficacy Study of Imiquimod 5% Cream Applied 3x Per Week for 8 or 12 Weeks in Low Risk Nodular Basal Cell Carcinoma
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized Open Label Study to Evaluate the Safety and Efficacy if Imiquimod 5% Cream Applied 3 Times Per Week for 8 or 12 Weeks in the Treatment of Low Risk Nodular Basal Cell Carcinoma|
- Evaluate the clearance rate, defined as the proportion of subjects who are clinically and histologically clear of BCC at the treated nodular BCC target tumor site at the 8 week post-treatment visit
- intensity of local skin reactions such as erythema, vesicles, scarring [ Time Frame: every 4 weeks during treatment ] [ Designated as safety issue: Yes ]
- Cosmetic outcome [ Time Frame: 8 weeks posttreamnt ] [ Designated as safety issue: No ]
|Study Start Date:||January 2002|
|Study Completion Date:||September 2005|
Basal cell carcinoma (BCC) is a malignant skin cancer that is believed to develop from the basal layer of the epidermis. Ultraviolet (UV) radiation is the primary cause of BCC. It induces local and systemic immuno-suppression, p53 mutations, pyrimidine covalent dimers in desoxyribonucleic acid (DNA), and bcl-2 overexpression. All of these UV-induced changes are believed to be critical in the pathogenesis of BCC.
Topical application of imiquimod induces local interferon-alpha (IFN-alpha), interleukin-12 (IL-12), and tumor necrosis factor-alpha (TNF-alpha), with a resulting cytokine cascade that may induce and/or support a cytotoxic T-lymphocyte (Th1) immune response. Intralesional IFN-alpha has been shown to be effective for the treatment of BCC. Imiquimod may be an effective therapy for BCC.
Results from a pilot study demonstrated that topical imiquimod could clear superficial and nodular BCCs. Three phase II dose response studies in subjects with nodular BCC (nBCC) showed that the histological cure rates with imiquimod depend on the doses applied per week and the duration of treatment. Daily dosing or 5 times per week applications showed higher total clearance rates than 3 times per week dosing or less frequent dosing. Furthermore, a 12 week treatment period resulted in better efficacy results than a duration of only 6 weeks. On the other hand, local skin reactions increased with the doses applied per week. So a prolonged treatment period of 8 or 12 weeks with an application frequence of 3 times a week seems to be a good compromise between efficacy and safety.
The current safety and efficacy study of imiquimod 5% cream in the treatment of nodular basal cell carcinoma (nBCC) will use a composite endpoint including both a clinical (visual) assessment of the target tumor site and a histological evaluation of an excisional surgery taken from the target tumor site for primary assessment of complete tumor clearance 8 weeks post treatment.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00204555
|Skin Cancer Program, Department of Dermatology, Liebermeisterstrasse 8|
|Tübingen, BW, Germany, 72076|
|Principal Investigator:||Claus Garbe, MD||Skin Cancer Program, Department of Dermatology, University Hospital Tübingen|