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

Primary Purpose

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

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Vehicle
LDE225 0.25%
LDE225 0.75%
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Treatment for Basal Cell Carcinomas (BCCs) in Gorlin Syndrome Patients focused on measuring Basal Cell Carcinoma, Gorlin Syndrome,, Gorlin-Goltz Syndrome,, Basal Cell Nevus Syndrome,, Nevoid Basal Cell Carcinoma Syndrome,, Basal Cell Carcinoma Nevus Syndrome

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigator Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Placebo Comparator

Active Comparator

Active Comparator

Arm Label

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

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

LDE225 0.25% [Part II]

LDE225 0.75% [Part II]

Arm Description

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.

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.

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

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.

Outcomes

Primary Outcome Measures

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).
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).

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
August 18, 2009
Last Updated
October 5, 2015
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00961896
Brief Title
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

2. Study Status

Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LDE225 (applied in parallel with vehicle) [Part I]
Arm Type
Active Comparator
Arm Description
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 Title
Vehicle cream (applied in parallel with LDE225 [Part I]
Arm Type
Placebo Comparator
Arm Description
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 Title
LDE225 0.25% [Part II]
Arm Type
Active Comparator
Arm Description
Participants were exposed to topically applied 0.25% LDE225 cream twice daily for 6 weeks.
Arm Title
LDE225 0.75% [Part II]
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Vehicle
Intervention Description
Placebo cream
Intervention Type
Drug
Intervention Name(s)
LDE225 0.25%
Intervention Type
Drug
Intervention Name(s)
LDE225 0.75%
Primary Outcome Measure Information:
Title
Percentage of BCCs With Complete and at Least Partial Clinical Clearance
Description
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).
Time Frame
4 weeks, 6 weeks, 9 weeks
Title
Number of Participants With at Least Partial Clinical Clearance (Part I)
Description
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).
Time Frame
day 8, day 15, day 22, day 29
Secondary Outcome Measure Information:
Title
Change From Baseline in Tumor Measurements (Part I)
Description
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.
Time Frame
4 weeks
Title
Change From Baseline in Tumor Measurements (Part II)
Description
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.
Time Frame
4 weeks, 6 weeks, 9 weeks
Title
Change From Baseline in Tumor Measurements (by Tumor) (Part I)
Description
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.
Time Frame
4 weeks
Title
Change From Baseline in Tumor Measurements (by Tumor) (Part II)
Description
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.
Time Frame
4 weeks, 6 weeks, 9 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Graz
Country
Austria
Facility Name
Novartis Investigator Site
City
Vienna
Country
Austria
Facility Name
Novartis Investigative Site
City
Zurich
Country
Switzerland

12. IPD Sharing Statement

Learn more about this trial

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

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