Treatment for Basal Cell Carcinomas (BCCs) in Gorlin Syndrome PatientsPhase 2NCT00961896

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

A Phase 2 study testing LDE225 0.25% and LDE225 0.75% in people with Treatment for Basal Cell Carcinomas (BCCs) in Gorlin Syndrome Patients, run by Novartis Pharmaceuticals at 3 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Treatment for Basal Cell Carcinomas (BCCs) in Gorlin Syndrome Patients
What is being tested?: LDE225 0.25% and LDE225 0.75%
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 18 participants
Where: 3 sitesin 2 countries
Study dates: Jul 2009to Aug 2010
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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.

Trial locations and contacts

3 sites in 2 countries.

Country

City, postcode or hospital

3 sites in 2 countries

Austria2 sites

Novartis Investigative Site
Graz
Novartis Investigator Site
Vienna

Other trials in Austria

Switzerland1 site

Novartis Investigative Site
Zurich

Other trials in Switzerland

About this study

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

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
Being tested: Vehicle, LDE225 0.25%, LDE225 0.75%
Keywords: Basal Cell Carcinoma, Gorlin Syndrome,, Gorlin-Goltz Syndrome,, Basal Cell Nevus Syndrome,, Nevoid Basal Cell Carcinoma Syndrome,, Basal Cell Carcinoma Nevus Syndrome
Medical subject headings: Carcinoma, Basal Cell, Basal Cell Nevus Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VehicleDrug
Placebo cream
LDE225 0.25%Drug
LDE225 0.75%Drug

Study groups in NCT00961896
Study group	Role	What they receive
LDE225 (applied in parallel with vehicle) [Part I]	Active comparator	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. Receives: Drug: LDE225 0.75%
Vehicle cream (applied in parallel with LDE225 [Part I]	Placebo comparator	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. Receives: Drug: Vehicle
LDE225 0.25% [Part II]	Active comparator	Participants were exposed to topically applied 0.25% LDE225 cream twice daily for 6 weeks. Receives: Drug: LDE225 0.25%
LDE225 0.75% [Part II]	Active comparator	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. Receives: Drug: LDE225 0.75%

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 4 weeks, 6 weeks, 9 weeks
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).
Measured: day 8, day 15, day 22, day 29

Secondary outcomes (4)

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.
Measured: 4 weeks
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.
Measured: 4 weeks, 6 weeks, 9 weeks
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.
Measured: 4 weeks
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.
Measured: 4 weeks, 6 weeks, 9 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2009Aug 2010

First posted19 Aug 2009 (estimated)
Study startJul 2009
Primary completionAug 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Treatment for Basal Cell Carcinomas (BCCs) in Gorlin Syndrome PatientsStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00961896
Sponsor's protocol ID: CLDE225B2203
Other IDs: EudraCT 2008 005506-40
Status last verified: Oct 2015
First submitted: 18 Aug 2009
Last updated: 3 Nov 2015
Results posted: Yes, on ClinicalTrials.gov

Study at a glance

From the registry record, last updated by the sponsor on 3 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00961896
Acronym / sponsor ID: CLDE225B2203
Conditions: 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
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Jul 2009
Primary completion: Aug 2010 (actual)
First posted: 19 Aug 2009 (estimated)
Results: Posted 21 Sep 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
LDE225 (applied in parallel with vehicle) [Part I]	Active comparator	Drug: 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 cream (applied in parallel with LDE225 [Part I]	Placebo comparator	Drug: VehicleParticipants 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 0.25% [Part II]	Active comparator	Drug: LDE225 0.25%Participants were exposed to topically applied 0.25% LDE225 cream twice daily for 6 weeks.
LDE225 0.75% [Part II]	Active comparator	Drug: LDE225 0.75%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.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

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

Key exclusion criteria (3 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VehiclePlacebo cream	Drug	Vehicle cream (applied in parallel with LDE225 [Part I]
LDE225 0.25%	Drug	LDE225 0.25% [Part II]
LDE225 0.75%	Drug	LDE225 (applied in parallel with vehicle) [Part I], LDE225 0.75% [Part II]

Primary outcome

Percentage of BCCs With Complete and at Least Partial Clinical Clearance
Time frame: 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)
Time frame: 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).

4 secondary outcomes

Change From Baseline in Tumor Measurements (Part I)
Time frame: 4 weeks
Change From Baseline in Tumor Measurements (Part II)
Time frame: 4 weeks, 6 weeks, 9 weeks
Change From Baseline in Tumor Measurements (by Tumor) (Part I)
Time frame: 4 weeks
Change From Baseline in Tumor Measurements (by Tumor) (Part II)
Time frame: 4 weeks, 6 weeks, 9 weeks

Results and safety

Results posted to the registry on 21 Sep 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
All Part I Participants	8	8
LDE225 0.25% [Part II]	3	3
LDE225 0.75% [Part II]	7	6

Primary outcome: Percentage of BCCs With Complete and at Least Partial Clinical Clearance

Time frame: 4 weeks, 6 weeks, 9 weeks. Number. Unit: Percentage of BCCs

Measure	LDE225 (Applied in Parallel With Vehicle) [Part I] n = 8	Vehicle Cream (Applied in Parallel With LDE225 [Part I] n = 8	LDE225 0.25% [Part II] n = 3	LDE225 0.75% [Part II] n = 7
Week 4, at least partial	92	7	83	77
Week 4, complete	23	0	0	0
Week 6, at least partial	NA	NA	83	96
Week 6, complete	NA	NA	0	0
Week 9, at least partial (LDE 0.75%, n=10)	NA	NA	NA	100
Week 9, complete (LDE 0.75%, n=10)	NA	NA	NA	0

Population analysed: All participants were analyzed.

Primary outcome: Number of Participants With at Least Partial Clinical Clearance (Part I)

Time frame: day 8, day 15, day 22, day 29. Number. Unit: Number of participants

Measure	LDE225 (Applied in Parallel With Vehicle) [Part I] n = 8	Vehicle Cream (Applied in Parallel With LDE225 [Part I] n = 8
Day 8	5	1
Day 15	7	2
Day 22	8	1
Day 29	8	1

Population analysed: All part I participants were included in the analysis.

4 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
All Part I Participants	0 of 8 (0%)	7 of 8 (87.5%)	Not reported
0.25% LDE225 [Part II]	0 of 3 (0%)	2 of 3 (66.7%)	Not reported
0.75% LDE225 [Part II]	1 of 7 (14.3%)	5 of 7 (71.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

3 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LDE225 0.25% and LDE225 0.75% in people with Treatment for Basal Cell Carcinomas (BCCs) in Gorlin Syndrome Patients, run by Novartis Pharmaceuticals at 3 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Austria, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of BCCs With Complete and at Least Partial Clinical Clearance (time frame: 4 weeks, 6 weeks, 9 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00961896.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2015.