Efficacy, Safety and Pharmacokinetics of Oral LDE225 in Treatment of Patients With Nevoid Basal Cell Carcinoma Syndrome (NBCCS)

This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
First received: May 6, 2011
Last updated: September 23, 2015
Last verified: September 2015
This was a phase II, double-blind, randomized, proof-of-concept, dose-ranging trial evaluating the efficacy, safety and pharmacokinetics of oral LDE225 in treatment of adult patients with NBCCS. This was an exploratory study designed to demonstrate preliminary efficacy of LDE225 in this indication. This study included a Screening period of approximately 4 weeks, treatment period duration of 12 weeks with initial follow-up of approximately 6-8 weeks followed by a long-term follow-up period.

Condition Intervention Phase
Basal Cell Carcinoma
Gorlin Syndrome
Nevoid Basal Cell Carcinoma Syndrome
Drug: LDE225
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II, Double-blind, Randomized, Proof-of-Concept, Dose-ranging Trial Evaluating the Efficacy, Safety and Pharmacokinetics of Oral LDE225 in Treatment of Adult Patients With Nevoid Basal Cell Carcinoma Syndrome

Resource links provided by NLM:

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Clinical Clearance Assessment of Main Target Basal Cell Carcinomas (BCCs) [ Time Frame: Day 113 ] [ Designated as safety issue: No ]
    The clinical response of the main target (and secondary target, as appropriate) BCC(s) to treatment was evaluated using the following 6-point scale comparing the assessment at the visit to the clinical presentation at Baseline: 0 = Worsening, 1 = No change, 2 = Slight clearance (1-25% improvement), 3 = Moderate clearance (26-75% improvement), 4 = Marked clearance (76-99% improvement),5 = Complete clearance (100% improvement) Complete clearance was defined as no clinical residual signs of carcinoma, as evaluated by the Investigator at a post-Baseline visit, with the exception of post-inflammatory changes such as minimal residual erythema or residual hyper-pigmentation or hypo-pigmentation or residual scarring.

Secondary Outcome Measures:
  • Histological Clearance Assessment of Main Target BCCs [ Time Frame: day 113 ] [ Designated as safety issue: No ]
    The main (and secondary, if appropriate) target BCC tumor area(s) was/were excised surgically and sent to a central laboratory for histological examination.

  • Measure: Disease Burden by BCC Tumor Counts [ Time Frame: Baseline, day 85, and day 113 ] [ Designated as safety issue: No ]
    BCC tumor counts were performed separately for five body regions: head and neck, trunk back, trunk front (including axillae and groin), upper extremities and lower extremities (including buttocks). During the counting, the BCC tumors, were categorized upon inspection by their longest diameter measurement (<10 mm, 10-19 mm, 20-29 mm, and >+30mm), and also by the type of BCC (superficial, nodular, other). The counts for all of the BCC type and size categories were determined (or estimated if many small lesions) for each body region. The body region counts were summated to provide the overall BCC tumor count.

Enrollment: 10
Study Start Date: April 2011
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: LDE225
Participants received 400 mg once daily.
Drug: LDE225
supplied as 100 mg capsules
Placebo Comparator: Placebo
Participants received matching placebo.
Drug: Placebo
supplied in capsules


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with multiple basal cell carcinomas (at least two) and typical presentation of NBCCS.
  • Female patients must be women of non-childbearing potential (WONCBP).

Exclusion Criteria:

  • Use of any topical treatment to treat BCCs, including prescription and over the counter in the 4 weeks prior to first dose of study drug.
  • Use of photodynamic therapy (PDT), radiation or systemic treatment known to affect BCCs or neoplasm in the 12 weeks prior to first dose of study drug.
  • Patients receiving medications that are recognized to cause rhabdomyolysis or patients with a prior history of rhabdomyolysis.
  • Patients with a histologically confirmed diagnosis of locally advanced or metastatic BCC.

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01350115

Novartis Investigative Site
Wien, Austria, A-1090
Novartis Investigative Site
Leuven, Belgium, 3000
Canada, Ontario
Novartis Investigative Site
Markham, Ontario, Canada, L3P 1A8
Novartis Investigative Site
Waterloo, Ontario, Canada, N2J 1C4
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H2K 4L5
Novartis Investigative Site
Kiel, Germany, 24105
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01350115     History of Changes
Other Study ID Numbers: CLDE225B2209, 2010-023819-34
Study First Received: May 6, 2011
Results First Received: August 18, 2015
Last Updated: September 23, 2015
Health Authority: Canada: Health Canada
Austria: Agency for Health and Food Safety
Germany: Federal Institute for Drugs and Medical Devices
Belgium: Federal Agency for Medicinal Products and Health Products

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
Smo inhibitor,
Hedgehog pathway inhibitor

Additional relevant MeSH terms:
Basal Cell Nevus Syndrome
Carcinoma, Basal Cell
Abnormalities, Multiple
Bone Cysts
Bone Diseases
Bone Diseases, Developmental
Congenital Abnormalities
Genetic Diseases, Inborn
Jaw Cysts
Jaw Diseases
Musculoskeletal Diseases
Neoplasms by Histologic Type
Neoplasms, Basal Cell
Neoplasms, Glandular and Epithelial
Neoplastic Syndromes, Hereditary
Odontogenic Cysts
Pathologic Processes
Stomatognathic Diseases

ClinicalTrials.gov processed this record on November 30, 2015