Nevoid Basal Cell carcinoma syndrome MedDRA version: 14.1 Level: LLT Classification code 10004151 Term: Basal cell nevus syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: LDE225
Product Code: LDE225
Pharmaceutical Form: Capsule, hard
Current Sponsor code: LDE225
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharm
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Typical presentation of NBCCS in the opinion of the investigator, based on clinical criteria; and patient meets at least one of the major diagnostic criteria for NBCCS. •Presence of multiple BCCs at the Screening visit. Patients will need to have at least two BCCs including a main target BCC and either a biomarker BCC or a secondary target BCC. Patients may have all three. These BCCs are defined as follows: • Main target BCC that is 5-20 mm in its longest dimension. This BCC must not be a recurring tumor, and must not have been previously treated nor biopsied. The lesion must be in a location (excluding the face) that is amenable, to both the investigator and the patient, to clinical excision with an approximately 4 mm margin of clinically uninvolved skin. There must be sufficient clinically uninvolved skin between the main target BCC and any other BCC to allow for excision without including or disturbing the other BCC. • Biomarker BCC that is 10-40 mm in its longest dimension. This BCC must not be a recurring tumor, and must not have been previously treated nor biopsied. The patient must be amenable to having this lesion biopsied with a 4 mm punch biopsy at Screening and at Week 4. • Secondary target BCC that is 5-20 mm in its longest dimension. This BCC may be on the face, must not be a recurring tumor, and must not have been previously treated nor biopsied. The lesion may be in a location that is amenable, to both the investigator and the patient, to clinical excision with an approximately 4 mm margin of clinically uninvolved skin. •Male or female patients, of any race or ethnicity, at least 18 years of age at time of informed consent. •Female patients must be women of non-childbearing potential (WONCBP). •Male patients who are fertile must be using two effective methods of contraception (e.g., spermicidal gel plus condom) for the entire duration of treatment and up to the Week 18 visit. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Identified main target, biomarker and secondary target BCCs must not be any type of BCC other than superficial or nodular; types excluded include sclerodermiform and BCCs with unclear diagnosis by clinical examination. •Patients with a histologically confirmed diagnosis of locally advanced or metastatic BCC that is not amenable to radiation therapy or curative surgery or have evidence of disease progression following radiotherapy. •Patients receiving medications that are recognized to cause rhabdomyolysis (e.g., HMG CoA reductase inhibitors (statins), clofibrate, and gemfibrozil), or patients with a prior history of rhabdomyolysis. •Regular strenuous exercise (e.g., long distance running, body building) that will be ongoing or occurring during treatment. •Require medical treatment with prohibited concomitant medication(s), or receiving dietary supplements, known to inhibit and/or to induce CYP3A4/5, or be a CYP2B6 substrate, in the four weeks or 5 half lives (whichever is longer) prior to first dose of study drug. • A Screening or Baseline/Day 1 12 lead ECG that demonstrates clinically relevant abnormalities which may affect patient safety or interpretation of study results. • Presence of unhealed bone fracture. Patients with recent bone fracture will be considered eligible if the fracture has healed, according to local standard of care, as assessed by both the principal investigator and the treating physician.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the efficacy of LDE225, as assessed by clinical clearance of a main target BCC (one per patient) in Nevoid Basal Cell Carcinoma Syndrome (NBCCS) patients;Secondary Objective: •To evaluate the efficacy of LDE225, as assessed by histological clearance of a main target BCC (one per patient) in NBCCS patients •To evaluate the effect of LDE225, as assessed by change in BCC tumor counts, on the total cutaneous burden of BCCs in NBCCS patients ;Primary end point(s): The primary variable will be the assessment of complete clinical clearance at any time up to and including 16 weeks post-baseline (the ‘excision timepoint’) for the main target BCC. Clinical clearance will be recorded on a six-point scale (see Section 6.4.1 of protocol). A score of 5 will be considered as complete clinical clearance. | — |
Countries
Austria, Belgium, Canada, Germany
Outcome results
None listed