Conditions: Treatment for Basal Cell Carcinomas (BCCs) in Gorlin Syndrome Patients
Keywords: Basal Cell Carcinoma Gorlin Syndrome, Gorlin-Goltz Syndrome, Basal Cell Nevus Syndrome, Nevoid Basal Cell Carcinoma Syndrome, Basal Cell Carcinoma Nevus Syndrome
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 18
Healthy volunteers: no

Brief summary:
Part I was 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 were exposed to multiple doses of topically applied LDE225 twice daily for 4 weeks in a double-blind manner. The patients returned weekly for visits where each BCC was clinically evaluated and digital photographs taken. Local safety and tolerability was also assessed. After the last application of treatment, biopsies were taken from treated (both vehicle and LDE225) BCCs (three per patient) for histology, biomarker evaluation and for pharmacokinetics (skin exposure). In addition, a biopsy from LDE225-treated uninvolved perilesional skin was taken for pharmacokinetic evaluation. In total, 4 biopsies were taken: 2 for histology and biomarker and 2 for PK.

Part II of this study consisted of a 21-day screening period, a baseline period (directly before commencing the treatment period) and a treatment period of 6 or 9 weeks, depending on randomization. A clinical assessment was performed on site on the last treatment day and if a full clinical response had been observed, approximately 3 weeks after the last treatment an excision of the BCC(s) would have been performed. The study completion visit occurred either 1 week after the excision (when this visit was planned) or 1 week after the last treatment. For a subset of patients, skin biopsies were collected on the last treatment day and an excision of a BCC was also performed at that same visit.

Detailed description:

Arms:
arm 1: Participants were exposed to both topically applied 0.75% LDE225 cream and LDE225 vehicle cream twice daily for 28 days where each treatment was randomized to two different test areas on each participant. arm 2: Participants were exposed to both topically applied 0.75% LDE225 cream and LDE225 vehicle cream twice daily for 28 days where each treatment was randomized to two different test areas on each participant. arm 3: Participants were exposed to topically applied 0.25% LDE225 cream twice daily for 6 weeks. arm 4: Participants were exposed to topically applied 0.75% LDE225 cream twice daily where some basal cell carcinomas (BCCs) were teated for 6 weeks and some BCCs were treated for 9 weeks.

Interventions: intervention 1: Vehicle intervention 2: LDE225 0.25% intervention 3: LDE225 0.75%
Intervention descriptions: intervention 1: Placebo cream intervention 2: None intervention 3: None

Protocol document: