A Trial to Evaluate the Safety, Local Tolerability, Pharmacokinetics and Pharmacodynamics of LDE225 on Skin Basal Cell Carcinomas in Gorlin Syndrome Patients

NCT ID: NCT00961896

Last Updated: 2015-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31

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.

Conditions

Treatment for Basal Cell Carcinomas (BCCs) in Gorlin Syndrome Patients

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

LDE225 (applied in parallel with vehicle) [Part I]

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.

Group Type: ACTIVE_COMPARATOR

LDE225 0.75%

Intervention Type: DRUG

Vehicle cream (applied in parallel with LDE225 [Part I]

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.

Group Type: PLACEBO_COMPARATOR

Vehicle

Intervention Type: DRUG

Placebo cream

LDE225 0.25% [Part II]

Participants were exposed to topically applied 0.25% LDE225 cream twice daily for 6 weeks.

Group Type: ACTIVE_COMPARATOR

LDE225 0.25%

Intervention Type: DRUG

LDE225 0.75% [Part II]

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.

Group Type: ACTIVE_COMPARATOR

LDE225 0.75%

Intervention Type: DRUG

Interventions

Vehicle

Placebo cream

Intervention Type: DRUG

LDE225 0.25%

Intervention Type: DRUG

LDE225 0.75%

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Graz, , Austria

Novartis Investigator Site

Vienna, , Austria

Novartis Investigative Site

Zurich, , Switzerland

Countries

Austria; Switzerland

Other Identifiers

EudraCT 2008 005506-40

Identifier Type: -

Identifier Source: secondary_id

CLDE225B2203

Identifier Type: -

Identifier Source: org_study_id