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Trial record 11 of 32 for:    "Nevoid basal cell carcinoma syndrome"

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00961896
Recruitment Status : Completed
First Posted : August 19, 2009
Results First Posted : September 21, 2015
Last Update Posted : November 3, 2015
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Treatment for Basal Cell Carcinomas (BCCs) in Gorlin Syndrome Patients
Interventions Drug: Vehicle
Drug: LDE225 0.25%
Drug: LDE225 0.75%
Enrollment 18
Recruitment Details  
Pre-assignment Details  
Arm/Group Title All Part I Participants LDE225 0.25% [Part II] LDE225 0.75% [Part II]
Hide Arm/Group 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.

LDE225 0.75%

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

LDE225 0.25%

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%

Period Title: Overall Study
Started 8 3 7
Completed 8 3 6
Not Completed 0 0 1
Reason Not Completed
Abnormal laboratory value             0             0             1
Arm/Group Title All Part I Participants LDE225 0.25% [Part II] LDE225 0.75% [Part II] Total
Hide Arm/Group 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.

LDE225 0.75%

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

LDE225 0.25%

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%

Total of all reporting groups
Overall Number of Baseline Participants 8 3 7 18
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 3 participants 7 participants 18 participants
50  (13.5) 52  (11.7) 48  (13.4) 50  (12.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 3 participants 7 participants 18 participants
Female
4
  50.0%
1
  33.3%
3
  42.9%
8
  44.4%
Male
4
  50.0%
2
  66.7%
4
  57.1%
10
  55.6%
1.Primary Outcome
Title Percentage of BCCs With Complete and at Least Partial Clinical Clearance
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were analyzed.
Arm/Group Title 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]
Hide Arm/Group 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.

LDE225 0.75%

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.

Vehicle: Placebo cream

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

LDE225 0.25%

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%

Overall Number of Participants Analyzed 8 8 3 7
Overall Number of Units Analyzed
Type of Units Analyzed: Tumors (BCCs)
13 14 12 22
Measure Type: Number
Unit of Measure: Percentage of BCCs
Week 4, at least partial 92 7 83 77
Week 4, complete 23 0 0 0
Week 6, at least partial NA [1]  NA [1]  83 96
Week 6, complete NA [1]  NA [1]  0 0
Week 9, at least partial (LDE 0.75%, n=10) NA [1]  NA [1]  NA [2]  100
Week 9, complete (LDE 0.75%, n=10) NA [1]  NA [1]  NA [2]  0
[1]
Treatment duration for Part I was 4 weeks only.
[2]
Treatment duration for Part II at LDE225 0.25% was 6 weeks only.
2.Primary Outcome
Title Number of Participants With at Least Partial Clinical Clearance (Part I)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All part I participants were included in the analysis.
Arm/Group Title LDE225 (Applied in Parallel With Vehicle) [Part I] Vehicle Cream (Applied in Parallel With LDE225 [Part I]
Hide Arm/Group 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.

LDE225 0.75%

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.

Vehicle: Placebo cream

Overall Number of Participants Analyzed 8 8
Measure Type: Number
Unit of Measure: Number of participants
Day 8 5 1
Day 15 7 2
Day 22 8 1
Day 29 8 1
3.Secondary Outcome
Title Change From Baseline in Tumor Measurements (Part I)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All part I participants were included in the analysis.
Arm/Group Title LDE225 (Applied in Parallel With Vehicle) [Part I] Vehicle Cream (Applied in Parallel With LDE225 [Part I]
Hide Arm/Group 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.

LDE225 0.75%

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.

Vehicle: Placebo cream

Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: Percent change in tumor measurement
2D surface area -38.4  (24.82) 9.6  (6.75)
3D surface area -35.3  (19.68) 7.0  (16.86)
Height -32.3  (25.51) -13.2  (12.47)
Redness -4.8  (16.47) 1.2  (6.99)
Total volume -53.4  (30.85) -9.9  (17.21)
4.Secondary Outcome
Title Change From Baseline in Tumor Measurements (Part II)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Part II participants with evaluable data (n=3,6) were included in the analysis.
Arm/Group Title LDE225 0.25% [Part II] LDE225 0.75% [Part II]
Hide Arm/Group Description:
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 treated for 6 weeks and some BCCs were treated for 9 weeks.
Overall Number of Participants Analyzed 3 6
Mean (Standard Deviation)
Unit of Measure: percent change in tumor measurement
2D surface, week 4 -10.7  (16.81) -22.2  (40.43)
2D surface, week 6 -36.3  (12.51) -28.5  (43.64)
2D surface area, week 9 NA [1]   (NA) -26.0  (41.57)
3D surface area , week 4 -19.3  (4.62) -26.9  (33.29)
3D surface area, week 6 -31.7  (19.03) -35.2  (30.51)
3D surface area, week 9 NA [1]   (NA) -41.5  (30.05)
Total volume, week 4 -19.3  (27.82) -43.4  (36.25)
Total volume, week 6 -35.2  (37.99) -60.7  (22.11)
Total volume, week 9 NA [1]   (NA) -61.3  (31.18)
[1]
Treatment duration for the LDE225 0.25% arm was 6 weeks only.
5.Secondary Outcome
Title Change From Baseline in Tumor Measurements (by Tumor) (Part I)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All part I participants were included in this analysis.
Arm/Group Title LDE225 (Applied in Parallel With Vehicle) [Part I] Vehicle Cream (Applied in Parallel With LDE225 [Part I]
Hide Arm/Group 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.

LDE225 0.75%

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.

Vehicle: Placebo cream

Overall Number of Participants Analyzed 8 8
Overall Number of Units Analyzed
Type of Units Analyzed: Tumors (BCCs)
13 14
Mean (Standard Deviation)
Unit of Measure: Percent change in tumor measurement
2D surface area -40.8  (24.85) 10.6  (10.52)
3D surface area -34.5  (21.36) 8.7  (20.41)
Height -32.0  (26.97) -12.7  (18.93)
Redness -2.0  (22.50) 1.2  (7.42)
Total volume -49.8  (33.68) -9.1  (35.24)
6.Secondary Outcome
Title Change From Baseline in Tumor Measurements (by Tumor) (Part II)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Part II participants with evaluable data (n=3,6) were included in the analysis.
Arm/Group Title LDE225 0.25% [Part II] LDE225 0.75% [Part II]
Hide Arm/Group Description:
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 treated for 6 weeks and some BCCs were treated for 9 weeks.
Overall Number of Participants Analyzed 3 6
Overall Number of Units Analyzed
Type of Units Analyzed: Tumors (BCCs)
12 22
Mean (Standard Deviation)
Unit of Measure: Percent change in tumor measurement
2D surface area, week 4 -10.7  (24.23) -24.1  (30.69)
2D surface area, week 6 (LDE 0.75%, n=21) -36.3  (21.52) -33.3  (32.42)
2D surface area, week 9 (LDE 0.75%, n=10) NA [1]   (NA) -25.5  (35.71)
3D surface area, week 4 -19.3  (30.58) -23.1  (28.41)
3D surface area, week 6 (LDE 0.75%, n=21) -31.7  (31.19) -33.2  (23.63)
3D surface area, week 9 (LDE 0.75%, n=10) NA [1]   (NA) -38.0  (27.97)
Total volume, week 4 -19.3  (57.85) -38.3  (39.75)
Total volume, week 6 (LDE 0.75%, n=21) -35.2  (60.52) -56.8  (23.70)
Total volume, week 9 (LDE 0.75%, n=10) NA [1]   (NA) -58.0  (37.24)
[1]
Treatment duration for the LDE225 0.25% arm was 6 weeks only.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title All Part I Participants 0.25% LDE225 [Part II] 0.75% LDE225 [Part II]
Hide Arm/Group 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 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 treated for 6 weeks and some BCCs were treated for 9 weeks.
All-Cause Mortality
All Part I Participants 0.25% LDE225 [Part II] 0.75% LDE225 [Part II]
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
All Part I Participants 0.25% LDE225 [Part II] 0.75% LDE225 [Part II]
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   0/3 (0.00%)   1/7 (14.29%) 
Investigations       
HEPATIC ENZYME INCREASED  1  0/8 (0.00%)  0/3 (0.00%)  1/7 (14.29%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
All Part I Participants 0.25% LDE225 [Part II] 0.75% LDE225 [Part II]
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/8 (87.50%)   2/3 (66.67%)   5/7 (71.43%) 
Ear and labyrinth disorders       
EXTERNAL EAR INFLAMMATION  1  0/8 (0.00%)  0/3 (0.00%)  1/7 (14.29%) 
Eye disorders       
CONJUNCTIVITIS  1  0/8 (0.00%)  0/3 (0.00%)  1/7 (14.29%) 
General disorders       
FATIGUE  1  0/8 (0.00%)  0/3 (0.00%)  1/7 (14.29%) 
Infections and infestations       
INFECTION  1  0/8 (0.00%)  0/3 (0.00%)  1/7 (14.29%) 
NASOPHARYNGITIS  1  1/8 (12.50%)  0/3 (0.00%)  0/7 (0.00%) 
Injury, poisoning and procedural complications       
ARTHROPOD STING  1  1/8 (12.50%)  0/3 (0.00%)  0/7 (0.00%) 
INJURY CORNEAL  1  0/8 (0.00%)  0/3 (0.00%)  1/7 (14.29%) 
LIMB INJURY  1  1/8 (12.50%)  0/3 (0.00%)  0/7 (0.00%) 
Investigations       
BLOOD CHOLESTEROL INCREASED  1  1/8 (12.50%)  0/3 (0.00%)  0/7 (0.00%) 
BLOOD GLUCOSE INCREASED  1  1/8 (12.50%)  0/3 (0.00%)  0/7 (0.00%) 
BLOOD TRIGLYCERIDES INCREASED  1  1/8 (12.50%)  0/3 (0.00%)  0/7 (0.00%) 
GAMMA-GLUTAMYLTRANSFERASE INCREASED  1  1/8 (12.50%)  0/3 (0.00%)  0/7 (0.00%) 
GLUCOSE URINE PRESENT  1  1/8 (12.50%)  0/3 (0.00%)  0/7 (0.00%) 
HAEMATOCRIT DECREASED  1  0/8 (0.00%)  1/3 (33.33%)  0/7 (0.00%) 
HAEMOGLOBIN DECREASED  1  0/8 (0.00%)  1/3 (33.33%)  0/7 (0.00%) 
WHITE BLOOD CELLS URINE POSITIVE  1  2/8 (25.00%)  0/3 (0.00%)  0/7 (0.00%) 
Metabolism and nutrition disorders       
IRON DEFICIENCY  1  0/8 (0.00%)  1/3 (33.33%)  0/7 (0.00%) 
Musculoskeletal and connective tissue disorders       
ARTHRALGIA  1  1/8 (12.50%)  0/3 (0.00%)  0/7 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
ASTHMA  1  0/8 (0.00%)  1/3 (33.33%)  0/7 (0.00%) 
Skin and subcutaneous tissue disorders       
SKIN FISSURES  1  1/8 (12.50%)  0/3 (0.00%)  0/7 (0.00%) 
SKIN IRRITATION  1  4/8 (50.00%)  0/3 (0.00%)  1/7 (14.29%) 
URTICARIA  1  0/8 (0.00%)  0/3 (0.00%)  1/7 (14.29%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis
Phone: 862-778-8300
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00961896     History of Changes
Other Study ID Numbers: CLDE225B2203
EudraCT 2008 005506-40
First Submitted: August 18, 2009
First Posted: August 19, 2009
Results First Submitted: August 19, 2015
Results First Posted: September 21, 2015
Last Update Posted: November 3, 2015