Treatment for Basal Cell Carcinomas (BCCs) in Gorlin Syndrome Patients Clinical Trial
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
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.
| Status | Completed |
| Enrollment | 18 |
| Est. completion date | |
| Est. primary completion date | August 2010 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years to 75 Years |
| Eligibility |
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. |
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Austria | Novartis Investigative Site | Graz | |
| Austria | Novartis Investigator Site | Vienna | |
| Switzerland | Novartis Investigative Site | Zurich |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
Austria, Switzerland,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Clinical response parameters were defined as (i) complete response (i.e., there is no longer any visible evidence of a lesion consistent with BCC at this site), (ii) partial response (i.e., although a BCC still remains at this site, it has demonstrated a visible decrease in size compared with baseline), and (iii) no response / worsening (i.e., the BCC has not demonstrated any visible decrease in size compared with baseline). | 4 weeks, 6 weeks, 9 weeks | No |
| Primary | Number of Participants With at Least Partial Clinical Clearance (Part I) | Clinical response parameters were defined as (i) complete response (i.e., there is no longer any visible evidence of a lesion consistent with BCC at this site), (ii) partial response (i.e., although a BCC still remains at this site, it has demonstrated a visible decrease in size compared with baseline), and (iii) no response / worsening (i.e., the BCC has not demonstrated any visible decrease in size compared with baseline). | day 8, day 15, day 22, day 29 | No |
| Secondary | Change From Baseline in Tumor Measurements (Part I) | Measurement of the tumor size, volume and color by standardized digital photography, using dermatoscopic, macroscopic and 3D images of the BCCs was done by participant where if a participant had more than one tumor, for each of these tumors, the change from baseline was calculated (% change). From these values, the mean was calculated to get only one result per participant. Then for all the participants (n=8 both for LDE and vehicle), the mean was calculated. Photographic analysis was conducted by QuantifiCare. The volume of a lesion was measured with a special device, the "3D LIFEVIZ Micro system", which uses a lens splitter to produce two images of the skin surface, captured at the same time, with viewing angle differences close to human vision. A stereovision algorithm is then applied to reconstruct and quantitatively analyze the skin surface in 3D. A negative change from baseline indicates improvement. | 4 weeks | No |
| Secondary | Change From Baseline in Tumor Measurements (Part II) | Measurement of the tumor size, volume and color by standardized digital photography, using dermatoscopic, macroscopic and 3D images of the BCCs was done by participant where if a participant had more than one tumor, for each of these tumors, the change from baseline was calculated (% change). From these values, the mean was calculated to get only one result per participant. Then for all the participants (n=8 both for LDE and vehicle), the mean was calculated.. Photographic analysis was conducted by QuantifiCare. The volume of a lesion was measured with a special device, the "3D LIFEVIZ Micro system", which uses a lens splitter to produce two images of the skin surface, captured at the same time, with viewing angle differences close to human vision. A stereovision algorithm is then applied to reconstruct and quantitatively analyze the skin surface in 3D. A negative change from baseline indicates improvement. | 4 weeks, 6 weeks, 9 weeks | No |
| Secondary | Change From Baseline in Tumor Measurements (by Tumor) (Part I) | Measurement of the tumor size, volume and color by standardized digital photography, using dermatoscopic, macroscopic and 3D images of the BCCs. Photographic analysis was conducted by QuantifiCare. The volume of a lesion was measured with a special device, the "3D LIFEVIZ Micro system", which uses a lens splitter to produce two images of the skin surface, captured at the same time, with viewing angle differences close to human vision. A stereovision algorithm is then applied to reconstruct and quantitatively analyze the skin surface in 3D. A negative change from baseline indicates improvement. | 4 weeks | No |
| Secondary | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | Measurement of the tumor size, volume and color by standardized digital photography, using dermatoscopic, macroscopic and 3D images of the BCCs. Photographic analysis was conducted by QuantifiCare. The volume of a lesion was measured with a special device, the "3D LIFEVIZ Micro system", which uses a lens splitter to produce two images of the skin surface, captured at the same time, with viewing angle differences close to human vision. A stereovision algorithm is then applied to reconstruct and quantitatively analyze the skin surface in 3D. A negative change from baseline indicates improvement. | 4 weeks, 6 weeks, 9 weeks | No |