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

Purpose

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:

Genetics Home Reference related topics: Gillespie syndrome Gorlin syndrome focal dermal hypoplasia oculodentodigital dysplasia

Genetic and Rare Diseases Information Center resources: Nevoid Basal Cell Carcinoma Syndrome Gillespie Syndrome Oculodentodigital Dysplasia Focal Dermal Hypoplasia Focal Facial Dermal Dysplasia

U.S. FDA Resources

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

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations


Austria
Novartis Investigative Site
Wien, Austria, A-1090
Belgium
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
Germany
Novartis Investigative Site
Kiel, Germany, 24105

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators


Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information


Responsible Party:	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 BCCs

Additional relevant MeSH terms:


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

ClinicalTrials.gov processed this record on September 29, 2016