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

Purpose

This study is a double-blind, randomized, placebo-controlled Proof of Concept (PoC) study to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of oral LDE225 in treatment of skin basal cell carcinomas in patients with Nevoid Basal Cell Carcinoma Syndrome (NBCCS).

The core study starts after a screening period, and patients will be exposed to oral LDE225 once a day for 12 weeks in a double-blind manner. A long-term follow-up period for safety and disease burden assessment is planned after the end of the core study.

The study will be conducted in up to three treatment group cohorts at different doses, progressing to a subsequent cohort once data generated from a previous cohort provides rationale, based on safety and efficacy.

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: focal dermal hypoplasia Gillespie syndrome Gorlin syndrome oculodentodigital dysplasia

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

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Measure: Clinical evaluation of BCC tumors (complete response) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Measure: Histological signs of tumor regression; apoptosis; tumor proliferation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Measure: Disease burden by BCC tumor counts [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]


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	Drug: LDE225
Placebo Comparator: Placebo	Drug: Placebo

Eligibility


Ages Eligible for Study:	18 Years and older
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

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

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
Last Updated:	June 18, 2014
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:


Basal Cell Nevus Syndrome Carcinoma Carcinoma, Basal Cell Syndrome Abnormalities, Multiple Bone Cysts Bone Diseases Bone Diseases, Developmental Congenital Abnormalities Cysts Disease Genetic Diseases, Inborn	Jaw Cysts Jaw Diseases Musculoskeletal Diseases Neoplasms 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 March 01, 2015

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