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
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
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
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
Claus Garbe, MD
Skin Cancer Program, Department of Dermatology, University Hospital Tübingen
Germany: Federal Institute for Drugs and Medical Devices