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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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00961896
First received: August 18, 2009
Last updated: October 3, 2014
Last verified: October 2014
  Purpose

Part I is 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 will be exposed to multiple doses of topically applied LDE225 twice daily for 4 weeks in a double-blind manner. 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. After the last application of treatment, biopsies will be taken from treated BCCs (two per patient) 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.

Part II of this study will consist of a 21-day screening period, following which patients will be exposed to multiple doses of topically applied LDE225 twice daily for 6 or 9 weeks. Treatment will be topically applied (either 0.25% or 0.75% LDE225) twice daily in an open-label manner, with up to 4 BCCs treated per patient. 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. After the last application of treatment, one biopsy may be taken from a treated BCC for pharmacokinetics (skin drug exposure). In addition, a biopsy may be taken for pharmacokinetic evaluation of LDE225-treated uninvolved perilesional skin. In total, 2 biopsies may be taken. After the last treatment, a different treated BCC(s) may be excised surgically for histology and biomarker evaluation.


Condition Intervention Phase
Treatment for Basal Cell Carcinomas (BCCs) in Gorlin Syndrome Patients
Drug: Placebo
Drug: LDE225
Drug: LDE225 0.25%
Drug: LDE225 0.75%
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A 2-part, Randomized 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Clinical evaluation of BCC tumors (complete response) [ Time Frame: 4 weeks/6 weeks/9 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Measurement of the BCC tumor size, volume and color [ Time Frame: 4 weeks/6 weeks/9 weeks ] [ Designated as safety issue: No ]
  • Local toleration scoring scale [ Time Frame: 13 weeks ] [ Designated as safety issue: Yes ]
  • Histological signs of tumor regression; apoptosis, tumor proliferation [ Time Frame: 4 weeks/9-12 weeks ] [ Designated as safety issue: No ]
  • Biomarkers related to the Smo pathway [ Time Frame: 4 weeks/9-12 weeks ] [ Designated as safety issue: No ]
  • LDE225 pharmacokinetics in plasma and skin [ Time Frame: 4 weeks/6 weeks/9 weeks ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: July 2009
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: LDE225 and Vehicle (Applied in parallel) [Part I] Drug: Placebo
Active Comparator: Part I: LDE225 and Vehicle (Applied in parallel) [Part I] Drug: LDE225
Active Comparator: LDE225 0.25% [Part II] Drug: LDE225 0.25%
Active Comparator: LDE225 0.75% [Part II] Drug: LDE225 0.75%

  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 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Austria
Novartis Investigative Site
Graz, Austria
Novartis Investigator Site
Vienna, Austria
Switzerland
Novartis Investigative Site
Zurich, Switzerland
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00961896     History of Changes
Other Study ID Numbers: CLDE225B2203, EudraCT 2008 005506-40
Study First Received: August 18, 2009
Last Updated: October 3, 2014
Health Authority: Austria: Agency for Health and Food Safety
Switzerland: Swissmedic

Keywords provided by Novartis:
Basal Cell Carcinoma
Gorlin Syndrome,
Gorlin-Goltz Syndrome,
Basal Cell Nevus Syndrome,
Nevoid Basal Cell Carcinoma Syndrome,
Basal Cell Carcinoma Nevus Syndrome

Additional relevant MeSH terms:
Basal Cell Nevus Syndrome
Carcinoma
Carcinoma, Basal Cell
Craniofacial Abnormalities
Eye Abnormalities
Foot Deformities, Congenital
Syndactyly
Syndrome
Tooth Abnormalities
Abnormalities, Multiple
Bone Cysts
Bone Diseases
Bone Diseases, Developmental
Congenital Abnormalities
Cysts
Disease
Dysostoses
Eye Diseases
Foot Deformities
Genetic Diseases, Inborn
Jaw Cysts
Jaw Diseases
Limb Deformities, Congenital
Lower Extremity Deformities, Congenital
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Basal Cell
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 25, 2014