Part I is a double-blind, randomized, vehicle-controlled Proof of Concept (PoC) study to evaluate the safety, local tolerability, pharmacokinetics and pharmacodynamics of multiple topical administrations of LDE225 (a specific Smoothened inhibitor) on skin basal cell carcinomas in Gorlin's syndrome patients.

Following a 21-day screening period, patients will be exposed to multiple doses of topically applied LDE225 twice daily for 4 weeks in a double-blind manner. The patients will return weekly for visits where each BCC will be clinically evaluated and digital photographs taken. Local safety and tolerability will also be assessed. After the last application of treatment, biopsies will be taken from treated BCCs (two per patient) for histology, biomarker evaluation and for pharmacokinetics (skin exposure). In addition, a biopsy will be taken for pharmacokinetic evaluation of LDE225-treated uninvolved perilesional skin. In total, 4 biopsies will be taken.

Part II of this study will consist of a 21-day screening period, following which patients will be exposed to multiple doses of topically applied LDE225 twice daily for 6 or 9 weeks. Treatment will be topically applied (either 0.25% or 0.75% LDE225) twice daily in an open-label manner, with up to 4 BCCs treated per patient. The patients will return weekly for visits where each BCC will be clinically evaluated and digital photographs taken. Local safety and tolerability will also be assessed. After the last application of treatment, one biopsy may be taken from a treated BCC for pharmacokinetics (skin drug exposure). In addition, a biopsy may be taken for pharmacokinetic evaluation of LDE225-treated uninvolved perilesional skin. In total, 2 biopsies may be taken. After the last treatment, a different treated BCC(s) may be excised surgically for histology and biomarker evaluation.