Efficacy, Safety and Tolerability of Topically Applied LDE225 Cream (Hedgehog Pathway Inhibitor) in Adult Patients With Nevoid Basal Cell Carcinoma Syndrome (NBCCS)

A Randomized, Double-blind, Vehicle-controlled, Multicenter Trial of Topically Administered LDE225 Cream (0.75% Bid) to Evaluate Clearance of Basal Cell Carcinoma in Adult Patients With Nevoid Basal Cell Carcinoma Syndrome

This 22 week study will assess the efficacy, safety, and tolerability of LDE225 versus vehicle when applied topically to basal cell carcinoma (BCC) in patients with NBCCS. Patients will treat multiple BCCs for up to 12 weeks. Treatment success is defined as complete clinical clearance and complete histological clearance in BCCs.

Study Overview

• Status: Withdrawn
• Conditions: Basal Cell Carcinoma
• Intervention / Treatment: Drug: LDE225B; Drug: Vehicle

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium
    • Novartis Investigative Site
  • Leuven, Belgium
    • Novartis Investigative Site
• Canada
  • Ontario
    • Waterloo, Ontario, Canada
      • Novartis Investigative Site
  • Quebec
    • Sainte-Foy, Quebec, Canada
      • Novartis Investigative Site
• Czechia
  • Praha, Czechia
    • Novartis Investigative Site
• Finland
  • Helsinki, Finland
    • Novartis Investigative Site
• Germany
  • Berlin, Germany
    • Novartis Investigative Site
  • Bonn, Germany
    • Novartis Investigative Site
  • Dresden, Germany
    • Novartis Investigative Site
  • Essen, Germany
    • Novartis Investigative Site
  • Frankfurt, Germany
    • Novartis Investigative Site
  • Heidelberg, Germany
    • Novartis Investigative Site
  • Jena, Germany
    • Novartis Investigative Site
  • Kiel, Germany
    • Novartis Investigative Site
  • Luebeck, Germany
    • Novartis Investigative Site
  • Mainz, Germany
    • Novartis Investigative Site
  • Muenster, Germany
    • Novartis Investigative Site
  • Munich, Germany
    • Novartis Investigative Site
  • Recklinghausen, Germany
    • Novartis Investigative Site
  • Tuebingen, Germany
    • Novartis Investigative Site
  • Wuerzburg, Germany
    • Novartis Investigative Site
• Greece
  • Athens, Greece
    • Novartis Investigative Site
  • Thessaloniki, Greece
    • Novartis Investigative Site
• Italy
  • Catania, Italy
    • Novartis Investigative Site
  • L'Aquila, Italy
    • Novartis Investigative Site
  • Napoli, Italy
    • Novartis Investigative Site
  • Padova, Italy
    • Novartis Investigative Site
  • Siena, Italy
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain
    • Novartis Investigative Site
  • Madrid, Spain
    • Novartis Investigative Site
• Switzerland
  • Lausanne, Switzerland
    • Novartis Investigative Site
  • Zuerich, Switzerland
    • Novartis Investigative Site
• United Kingdom
  • Glasgow, United Kingdom
    • Novartis Investigative Site
  • London, United Kingdom
    • Novartis Investigative Site
  • Manchester, United Kingdom
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult greater than 18 years old, male or female.
2. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study.
3. Typical presentation of NBCCS in the opinion of the investigator
4. At least one of the major clinical criteria of NBCCS.
5. Multiple BCCs during the screening period

Exclusion Criteria:

1. Any concomitant dermatological disease that could confound the evaluations, based on the discretion of the investigator.
2. Prior exposure to LDE225.
3. Use of systemic treatment for BCC in the 4 weeks prior to Baseline.
4. Use of topical treatment or photodynamic therapy (PDT) in the 12 weeks prior to Baseline.
5. Use of other investigational drugs at Baseline, or within 30 days or 5 half-lives prior to Baseline, whichever is longer.
6. Clinically significant medical condition, as per judgment of the investigator.
7. History of hypersensitivity to any of the ingredient of the study drug.
8. Pregnant or nursing (lactating) women
9. Women of child-bearing potential and fertile males, UNLESS they are using two birth control methods

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Vehicle	Drug: Vehicle; cream, 2x daily
Active Comparator: LDE225 0.75% cream	Drug: LDE225B; Cream, 2x daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To demonstrate superiority of topical LDE225 versus vehicle in terms of treatment success in patients with NBCCs. Measure: Complete clinical clearance and complete histological clearance of BCCs	4 weeks after LDE225 treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the safety of topical treatment with LDE225, compared to vehicle. Measure: Reported systemic adverse events in patients with NBCCS	Treatment phase and up to 4 weeks after LDE225 treatment
To evaluate the local tolerability of topical treatment with LDE225, compared to vehicle. Measure:Reported local adverse events in patients with NBCCS	Treatment phase and up to 4 weeks after LDE225 treatment
To assess the rate of complete clinical clearance of BCCs in patients with NBCCS. Measure: No clinical residual signs of carcinoma	4 weeks after LDE225 treatment
To assess the rate of complete histological clearance of BCCs in patients with NBCCS. Measure: No residual tumor tissue	4 weeks after LDE225 treatment

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: December 7, 2022
• Primary Completion: December 7, 2022
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: July 6, 2010
• First Submitted That Met QC Criteria: February 28, 2017
• First Posted (Actual): March 3, 2017

Study Record Updates

• Last Update Posted (Actual): May 5, 2017
• Last Update Submitted That Met QC Criteria: May 3, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: topical; Basal cell carcinoma; Nevoid Basal Cell Carcinoma Syndrome; NBCCS, Gorlin syndrome; Gorlin-Goltz Syndrome; Basal Cell Nevus Syndrome; BCNS, Hedgehog pathway inhibitor; Smoothened
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease; Cysts; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Stomatognathic Diseases; Bone Diseases; Neoplastic Syndromes, Hereditary; Jaw Diseases; Abnormalities, Multiple; Bone Diseases, Developmental; Odontogenic Cysts; Jaw Cysts; Bone Cysts; Neoplasms, Basal Cell; Syndrome; Carcinoma; Basal Cell Nevus Syndrome; Carcinoma, Basal Cell
• Other Study ID Numbers: CLDE225B2307

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No