A Trial to Evaluate the Safety, Local Tolerability, Pharmacokinetics and Pharmacodynamics of LDE225 on Skin Basal Cell Carcinomas in Gorlin Syndrome Patients
Condition: Treatment for Basal Cell Carcinomas (BCCs) in Gorlin Syndrome Patients
MeSH terms: Carcinoma; Carcinoma, Basal Cell; Basal Cell Nevus Syndrome; Syndrome
Intervention: Vehicle; LDE225 0.25%; LDE225 0.75%
Intervention description: Placebo cream
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Basal Cell Carcinoma; Gorlin Syndrome,; Gorlin-Goltz Syndrome,; Basal Cell Nevus Syndrome,; Nevoid Basal Cell Carcinoma Syndrome,; Basal Cell Carcinoma Nevus Syndrome

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.
    

Eligibility criteria:

        Inclusion Criteria:

        - Patients with multiple basal cell carcinomas and Gorlin syndrome, or patients with
        multiple basal cell carcinomas and a mutation in the PTCH1 gene at chromosome 9q22.3

        Exclusion Criteria:

          -  Previous treatment of the BCC's that are selected for treatment.

          -  Any systemic treatment which is known to affect BCCs esp. cytostatic treatments,
             retinoids and photodynamic treatments.

        Other protocol defined Incl./Excl. criteria may apply.