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

Novartis Pharmaceuticals10 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Basal Cell Carcinoma Gorlin Syndrome Nevoid Basal Cell Carcinoma Syndrome

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (6)

Novartis Investigative Site

Vienna, Austria

Novartis Investigative Site

Leuven, Belgium

Novartis Investigative Site

Markham, Ontario, Canada

Novartis Investigative Site

Waterloo, Ontario, Canada

Novartis Investigative Site

Montreal, Quebec, Canada

Novartis Investigative Site

Kiel, Germany

Outcomes

Primary Outcomes

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.

Time frame: Day 113

Secondary Outcomes

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.

Time frame: 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.

Time frame: Baseline, day 85, and day 113