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

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

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.

Study Overview

• Status: Completed
• Conditions: Nevoid Basal Cell Carcinoma Syndrome; Basal Cell Carcinoma; Gorlin Syndrome
• Intervention / Treatment: Drug: LDE225; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, A-1090
    • Novartis Investigative Site
• Belgium
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Canada
  • Ontario
    • Markham, Ontario, Canada, L3P 1A8
      • Novartis Investigative Site
    • Waterloo, Ontario, Canada, N2J 1C4
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H2K 4L5
      • Novartis Investigative Site
• Germany
  • Kiel, Germany, 24105
    • 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:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Clearance Assessment of Main Target Basal Cell Carcinomas (BCCs)	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.	Day 113

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Histological Clearance Assessment of Main Target BCCs	The main (and secondary, if appropriate) target BCC tumor area(s) was/were excised surgically and sent to a central laboratory for histological examination.	day 113
Measure: Disease Burden by BCC Tumor Counts	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.	Baseline, day 85, and day 113

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: May 6, 2011
• First Submitted That Met QC Criteria: May 6, 2011
• First Posted (Estimate): May 9, 2011

Study Record Updates

• Last Update Posted (Estimate): October 19, 2015
• Last Update Submitted That Met QC Criteria: September 23, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Basal Cell Carcinoma; Hedgehog pathway inhibitor; Basal Cell Carcinoma Nevus Syndrome; Gorlin Syndrome,; Gorlin-Goltz Syndrome,; Basal Cell Nevus Syndrome,; Nevoid Basal Cell Carcinoma Syndrome,; Smo inhibitor,; BCCs
• 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: CLDE225B2209; 2010-023819-34 (EudraCT Number)