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

• ClinicalTrials.gov Identifier: NCT01350115
• Recruitment Status: Completed
• First Posted: May 9, 2011
• Results First Posted: October 19, 2015
• Last Update Posted: October 19, 2015
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Basal Cell Carcinoma; Gorlin Syndrome; Nevoid Basal Cell Carcinoma Syndrome	Drug: LDE225; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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
• Study Start Date: April 2011
• Actual Primary Completion Date: October 2012
• Actual Study Completion Date: October 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Clinical Clearance Assessment of Main Target Basal Cell Carcinomas (BCCs) [ Time Frame: 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 :

1. Histological Clearance Assessment of Main Target BCCs [ Time Frame: 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.
2. Measure: Disease Burden by BCC Tumor Counts [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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
• Other Study ID Numbers: CLDE225B2209; 2010-023819-34 ( EudraCT Number )
• First Posted: May 9, 2011
• Results First Posted: October 19, 2015
• Last Update Posted: October 19, 2015
• Last Verified: September 2015

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

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:

Carcinoma; Carcinoma, Basal Cell; Basal Cell Nevus Syndrome; 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