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

Phase 2

Completed

Conditions: Gorlin Syndrome
Nevoid Basal Cell Carcinoma Syndrome
Basal Cell Carcinoma

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants received matching placebo.
LDE225	LDE225	Participants received 400 mg once daily.

Primary Outcome Measures

Name	Time	Method
Clinical Clearance Assessment of Main Target Basal Cell Carcinomas (BCCs)	Day 113	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

Name	Time	Method
Histological Clearance Assessment of Main Target BCCs	day 113	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	Baseline, day 85, and day 113	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.