Clinical trial NCT00961896: A Trial to Evaluate the Safety, Local Tolerability, Pharmacokinetics and Pharmacodynamics of LDE225 on Skin Basal Cell Carcinomas in Gorlin Syndrome Patients
Official title: 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 Syndrome Patients Followed by an Open Label, Randomized Expansion Group to Test Two Different Strengths of an Improved LDE225 Formulation for Extended Treatment Durations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-08-19
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of BCCs With Complete and at Least Partial Clinical Clearance
timeFrame: 4 weeks, 6 weeks, 9 weeks
measure: Number of Participants With at Least Partial Clinical Clearance (Part I)
timeFrame: day 8, day 15, day 22, day 29
Secondary outcomes:
measure: Change From Baseline in Tumor Measurements (Part I)
timeFrame: 4 weeks
measure: Change From Baseline in Tumor Measurements (Part II)
timeFrame: 4 weeks, 6 weeks, 9 weeks
measure: Change From Baseline in Tumor Measurements (by Tumor) (Part I)
timeFrame: 4 weeks
measure: Change From Baseline in Tumor Measurements (by Tumor) (Part II)
timeFrame: 4 weeks, 6 weeks, 9 weeks
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Novartis Investigative Site
city: Vienna
country: Austria
facility: Novartis Investigator Site
city: Zurich
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: