A Trial to Evaluate the Safety, Local Tolerability, Pharmacokinetics and Pharmacodynamics of LDE225 on Skin Basal Cell Carcinomas in Gorlin's Syndrome Patients - Full Text View

Sponsor:	Novartis Pharmaceuticals
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00961896

Purpose

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.

The study will consist of a 21-day screening period, a baseline period (directly before commencing the treatment period) and a treatment period of 4 weeks followed by a safety visit one week after last study drug administration (week 5) and a Study Completion evaluation 4 weeks after the last study drug administration.

Patients will be exposed to multiple doses of topically applied LDE225 twice daily for 4 weeks in a double-blind manner. LDE225 and the vehicle as a negative control, will be randomized to the test areas. Following the last application of the treatment, biopsies will be taken from the BCCs for histology, biomarker evaluation and for pharmacokinetics (skin exposure). In addition, a biopsy will be taken for pharmacokinetic evaluation of LDE225-treated uninvolved perilesional skin. In total, 4 biopsies will be taken.

The patients will return weekly for visits where each BCC will be clinically evaluated and digital photographs taken. Local safety and tolerability will also be assessed.

Condition	Intervention	Phase
Basal Cell Carcinomas Gorlin's Syndrome	Drug: LDE225 Drug: Vehicle	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Single Group Assignment
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's Syndrome Patients

Resource links provided by NLM:

Genetics Home Reference related topics: Gorlin syndrome Help Me Understand Genetics

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Clinical evaluation of BCC tumors (complete response, partial response, no response / worsening) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Measurement of the BCC tumor size, volume and color by standardized digital photography [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Local toleration scoring scale [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
Histological signs of tumor regression; apoptosis, tumor proliferation markers in BCC [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Specific biomarkers related to the Smo pathway (Gli1, Gli2, Ptch1 and Ptch2) in BCC tumor tissue and expression of Gli1 by immunohistochemistry [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
LDE225 pharmacokinetics in plasma and skin [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	8
Study Start Date:	July 2009
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Vehicle: Placebo Comparator LDE225 and Vehicle (Applied in parallel)	Drug: Vehicle
LDE225: Active Comparator LDE225 and Vehicle (Applied in parallel)	Drug: LDE225

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with multiple basal cell carcinomas and Gorlin's syndrome fulfilling the diagnostic criteria, or patients suffering from multiple basal cell carcinomas and a mutation in the PTCH1 gene at chromosome 9q22.3, will be included.
Patients need to have at least 2 different body areas (scalp, arm, frontal trunk or posterior trunk and legs ) with basal cell carcinoma(s): one basal cell carcinoma >10 mm diameter, or 2 basal cell carcinomas > 5 mm diameter.

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00961896

Contacts

Contact: Novartis Pharmaceuticals

+41-61-324-1111

Locations

Austria
Novartis Investigator Site	Recruiting
Vienna, Austria

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Novartis Pharmaceuticals ( External Affairs )
Study ID Numbers:	CLDE225B2203, EudraCT 2008 005506-40
Study First Received:	August 18, 2009
Last Updated:	August 18, 2009
ClinicalTrials.gov Identifier:	NCT00961896 History of Changes
Health Authority:	Austria: Agency for Health and Food Safety

Keywords provided by Novartis:

Basal cell carcinomas
Gorlin's syndrome
Treatment on basal cell carcinomas in Gorlin's syndrome patients

Additional relevant MeSH terms:

Disease
Neoplasms by Histologic Type
Jaw Diseases
Carcinoma, Basal Cell
Jaw Cysts
Cysts
Bone Diseases
Carcinoma
Basal Cell Nevus Syndrome
Odontogenic Cysts
Neoplasms
Pathologic Processes

Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
Musculoskeletal Diseases
Syndrome
Bone Cysts
Abnormalities, Multiple
Bone Diseases, Developmental
Neoplasms, Basal Cell
Stomatognathic Diseases
Congenital Abnormalities
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on February 08, 2010