Treatment for Basal Cell Carcinomas (BCCs) in Gorlin Syndrome Patients
Conditions
Keywords
Basal Cell Carcinoma, Gorlin Syndrome,, Gorlin-Goltz Syndrome,, Basal Cell Nevus Syndrome,, Nevoid Basal Cell Carcinoma Syndrome,, Basal Cell Carcinoma Nevus Syndrome
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.
Interventions
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of BCCs With Complete and at Least Partial Clinical Clearance | 4 weeks, 6 weeks, 9 weeks | 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) | day 8, day 15, day 22, day 29 | 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
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Tumor Measurements (Part I) | 4 weeks | 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) | 4 weeks, 6 weeks, 9 weeks | 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) | 4 weeks | 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) | 4 weeks, 6 weeks, 9 weeks | 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. |
Countries
Austria, Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Part I Participants 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.
LDE225 0.75% | 8 |
| LDE225 0.25% [Part II] Participants were exposed to topically applied 0.25% LDE225 cream twice daily for 6 weeks.
LDE225 0.25% | 3 |
| LDE225 0.75% [Part II] Participants were exposed to topically applied 0.75% LDE225 cream twice daily where some basal cell carcinomas (BCCs) were treated for 6 weeks and some BCCs were treated for 9 weeks.
LDE225 0.75% | 7 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Abnormal laboratory value | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | All Part I Participants | LDE225 0.25% [Part II] | LDE225 0.75% [Part II] | Total |
|---|---|---|---|---|
| Age, Continuous | 50 Years STANDARD_DEVIATION 13.5 | 52 Years STANDARD_DEVIATION 11.7 | 48 Years STANDARD_DEVIATION 13.4 | 50 Years STANDARD_DEVIATION 12.9 |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 8 | 2 / 3 | 5 / 7 |
| serious Total, serious adverse events | 0 / 8 | 0 / 3 | 1 / 7 |
Outcome results
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).
Time frame: day 8, day 15, day 22, day 29
Population: All part I participants were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Number of Participants With at Least Partial Clinical Clearance (Part I) | Day 8 | 5 Number of participants |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Number of Participants With at Least Partial Clinical Clearance (Part I) | Day 15 | 7 Number of participants |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Number of Participants With at Least Partial Clinical Clearance (Part I) | Day 22 | 8 Number of participants |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Number of Participants With at Least Partial Clinical Clearance (Part I) | Day 29 | 8 Number of participants |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Number of Participants With at Least Partial Clinical Clearance (Part I) | Day 29 | 1 Number of participants |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Number of Participants With at Least Partial Clinical Clearance (Part I) | Day 8 | 1 Number of participants |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Number of Participants With at Least Partial Clinical Clearance (Part I) | Day 22 | 1 Number of participants |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Number of Participants With at Least Partial Clinical Clearance (Part I) | Day 15 | 2 Number of participants |
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).
Time frame: 4 weeks, 6 weeks, 9 weeks
Population: All participants were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 4, at least partial | 92 Percentage of BCCs |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 4, complete | 23 Percentage of BCCs |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 6, at least partial | NA Percentage of BCCs |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 6, complete | NA Percentage of BCCs |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 9, at least partial (LDE 0.75%, n=10) | NA Percentage of BCCs |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 9, complete (LDE 0.75%, n=10) | NA Percentage of BCCs |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 9, complete (LDE 0.75%, n=10) | NA Percentage of BCCs |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 6, complete | NA Percentage of BCCs |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 4, at least partial | 7 Percentage of BCCs |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 6, at least partial | NA Percentage of BCCs |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 4, complete | 0 Percentage of BCCs |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 9, at least partial (LDE 0.75%, n=10) | NA Percentage of BCCs |
| LDE225 0.25% [Part II] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 4, complete | 0 Percentage of BCCs |
| LDE225 0.25% [Part II] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 6, at least partial | 83 Percentage of BCCs |
| LDE225 0.25% [Part II] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 6, complete | 0 Percentage of BCCs |
| LDE225 0.25% [Part II] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 9, complete (LDE 0.75%, n=10) | NA Percentage of BCCs |
| LDE225 0.25% [Part II] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 9, at least partial (LDE 0.75%, n=10) | NA Percentage of BCCs |
| LDE225 0.25% [Part II] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 4, at least partial | 83 Percentage of BCCs |
| LDE225 0.75% [Part II] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 9, at least partial (LDE 0.75%, n=10) | 100 Percentage of BCCs |
| LDE225 0.75% [Part II] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 9, complete (LDE 0.75%, n=10) | 0 Percentage of BCCs |
| LDE225 0.75% [Part II] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 4, complete | 0 Percentage of BCCs |
| LDE225 0.75% [Part II] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 6, complete | 0 Percentage of BCCs |
| LDE225 0.75% [Part II] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 4, at least partial | 77 Percentage of BCCs |
| LDE225 0.75% [Part II] | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Week 6, at least partial | 96 Percentage of BCCs |
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.
Time frame: 4 weeks
Population: All part I participants were included in this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part I) | 3D surface area | -34.5 Percent change in tumor measurement | Standard Deviation 21.36 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part I) | Redness | -2.0 Percent change in tumor measurement | Standard Deviation 22.5 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part I) | Height | -32.0 Percent change in tumor measurement | Standard Deviation 26.97 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part I) | Total volume | -49.8 Percent change in tumor measurement | Standard Deviation 33.68 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part I) | 2D surface area | -40.8 Percent change in tumor measurement | Standard Deviation 24.85 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part I) | Total volume | -9.1 Percent change in tumor measurement | Standard Deviation 35.24 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part I) | 2D surface area | 10.6 Percent change in tumor measurement | Standard Deviation 10.52 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part I) | 3D surface area | 8.7 Percent change in tumor measurement | Standard Deviation 20.41 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part I) | Height | -12.7 Percent change in tumor measurement | Standard Deviation 18.93 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part I) | Redness | 1.2 Percent change in tumor measurement | Standard Deviation 7.42 |
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.
Time frame: 4 weeks, 6 weeks, 9 weeks
Population: Part II participants with evaluable data (n=3,6) were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | 2D surface area, week 6 (LDE 0.75%, n=21) | -36.3 Percent change in tumor measurement | Standard Deviation 21.52 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | 3D surface area, week 9 (LDE 0.75%, n=10) | NA Percent change in tumor measurement | — |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | 3D surface area, week 4 | -19.3 Percent change in tumor measurement | Standard Deviation 30.58 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | Total volume, week 4 | -19.3 Percent change in tumor measurement | Standard Deviation 57.85 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | 2D surface area, week 9 (LDE 0.75%, n=10) | NA Percent change in tumor measurement | — |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | Total volume, week 6 (LDE 0.75%, n=21) | -35.2 Percent change in tumor measurement | Standard Deviation 60.52 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | 3D surface area, week 6 (LDE 0.75%, n=21) | -31.7 Percent change in tumor measurement | Standard Deviation 31.19 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | Total volume, week 9 (LDE 0.75%, n=10) | NA Percent change in tumor measurement | — |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | 2D surface area, week 4 | -10.7 Percent change in tumor measurement | Standard Deviation 24.23 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | Total volume, week 9 (LDE 0.75%, n=10) | -58.0 Percent change in tumor measurement | Standard Deviation 37.24 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | 2D surface area, week 4 | -24.1 Percent change in tumor measurement | Standard Deviation 30.69 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | 2D surface area, week 6 (LDE 0.75%, n=21) | -33.3 Percent change in tumor measurement | Standard Deviation 32.42 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | 2D surface area, week 9 (LDE 0.75%, n=10) | -25.5 Percent change in tumor measurement | Standard Deviation 35.71 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | 3D surface area, week 4 | -23.1 Percent change in tumor measurement | Standard Deviation 28.41 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | 3D surface area, week 6 (LDE 0.75%, n=21) | -33.2 Percent change in tumor measurement | Standard Deviation 23.63 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | 3D surface area, week 9 (LDE 0.75%, n=10) | -38.0 Percent change in tumor measurement | Standard Deviation 27.97 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | Total volume, week 4 | -38.3 Percent change in tumor measurement | Standard Deviation 39.75 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | Total volume, week 6 (LDE 0.75%, n=21) | -56.8 Percent change in tumor measurement | Standard Deviation 23.7 |
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.
Time frame: 4 weeks
Population: All part I participants were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (Part I) | 3D surface area | -35.3 Percent change in tumor measurement | Standard Deviation 19.68 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (Part I) | Redness | -4.8 Percent change in tumor measurement | Standard Deviation 16.47 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (Part I) | Height | -32.3 Percent change in tumor measurement | Standard Deviation 25.51 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (Part I) | Total volume | -53.4 Percent change in tumor measurement | Standard Deviation 30.85 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (Part I) | 2D surface area | -38.4 Percent change in tumor measurement | Standard Deviation 24.82 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (Part I) | Total volume | -9.9 Percent change in tumor measurement | Standard Deviation 17.21 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (Part I) | 2D surface area | 9.6 Percent change in tumor measurement | Standard Deviation 6.75 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (Part I) | 3D surface area | 7.0 Percent change in tumor measurement | Standard Deviation 16.86 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (Part I) | Height | -13.2 Percent change in tumor measurement | Standard Deviation 12.47 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (Part I) | Redness | 1.2 Percent change in tumor measurement | Standard Deviation 6.99 |
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.
Time frame: 4 weeks, 6 weeks, 9 weeks
Population: Part II participants with evaluable data (n=3,6) were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (Part II) | 2D surface, week 6 | -36.3 percent change in tumor measurement | Standard Deviation 12.51 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (Part II) | 3D surface area, week 9 | NA percent change in tumor measurement | — |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (Part II) | 3D surface area , week 4 | -19.3 percent change in tumor measurement | Standard Deviation 4.62 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (Part II) | Total volume, week 4 | -19.3 percent change in tumor measurement | Standard Deviation 27.82 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (Part II) | 2D surface area, week 9 | NA percent change in tumor measurement | — |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (Part II) | Total volume, week 6 | -35.2 percent change in tumor measurement | Standard Deviation 37.99 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (Part II) | 3D surface area, week 6 | -31.7 percent change in tumor measurement | Standard Deviation 19.03 |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (Part II) | Total volume, week 9 | NA percent change in tumor measurement | — |
| LDE225 (Applied in Parallel With Vehicle) [Part I] | Change From Baseline in Tumor Measurements (Part II) | 2D surface, week 4 | -10.7 percent change in tumor measurement | Standard Deviation 16.81 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (Part II) | Total volume, week 9 | -61.3 percent change in tumor measurement | Standard Deviation 31.18 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (Part II) | 2D surface, week 4 | -22.2 percent change in tumor measurement | Standard Deviation 40.43 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (Part II) | 2D surface, week 6 | -28.5 percent change in tumor measurement | Standard Deviation 43.64 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (Part II) | 2D surface area, week 9 | -26.0 percent change in tumor measurement | Standard Deviation 41.57 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (Part II) | 3D surface area , week 4 | -26.9 percent change in tumor measurement | Standard Deviation 33.29 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (Part II) | 3D surface area, week 6 | -35.2 percent change in tumor measurement | Standard Deviation 30.51 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (Part II) | 3D surface area, week 9 | -41.5 percent change in tumor measurement | Standard Deviation 30.05 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (Part II) | Total volume, week 4 | -43.4 percent change in tumor measurement | Standard Deviation 36.25 |
| Vehicle Cream (Applied in Parallel With LDE225 [Part I] | Change From Baseline in Tumor Measurements (Part II) | Total volume, week 6 | -60.7 percent change in tumor measurement | Standard Deviation 22.11 |