Gorlin syndrome
Conditions
Interventions
Product Code: LDE225
Pharmaceutical Form: Cream
Current Sponsor code: LDE225
Concentration unit: % (W/V) percent weight/volume
Concentration type: equal
Concentration number: 0.25-0.75
Sponsors
Novartis Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patients with multiple basal cell carcinomas and Gorlin’s syndrome fulfilling the diagnostic criteria, or patients suffering from multiple basal cell carcinomas and a mutation in the PTCH1 gene at chromosome 9q22.3, age 18 to 75 years, will be included. 2. Patients need to have a minimum of 2 BCCs (scalp, arm, frontal trunk or posterior trunk and legs, no face BCCs ). The basal cell carcinoma(s) should be > 4mm and 20 bpm) associated with clinical manifestation of postural hypotension. All blood pressure measurements at other time-points should be assessed with the subject seated, unless stated otherwise in the protocol design, and utilizing the same arm for each determination. 5.Postmenopausal females must have had no regular menstrual bleeding for at least one (1) year prior to initial dosing. Menopause will be confirmed by a plasma FSH level of >40 IU/L at screening. Female patients who report surgical sterilization must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the CRF. 6.Male patients must be using a two acceptable methods of contraception , (e.g., spermicidal gel plus condom) for the entire duration of the study, up to the Study Completion visit, and refrain from fathering a child in the three (3) (or greater if a long half-life drug) months following the last study drug administration. Periodic abstinence and withdrawal are not acceptable methods of contraception. 7.Patients must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 to 29 kg/m2. See Appendix 3 of this protocol for BMI ranges. 8.Able to communicate well with the investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent. Patients who have participated in the first part of the study can participate in Part II if they meet all inclusion/exclusion criteria for Part II. In order to be eligible, new BCC sites need to be identified. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 year
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria will be excluded from entry into or continuation in the study unless sponsor approval is obtained: 1.Previous treatment of the BCC’s that are selected for treatment with the study compound (LDE225) or the vehicle. 2.Use of any topical treatment whether prescribed or as on OTC on the treated areas during the course of the study. 3.Any systemic treatment which is known to affect BCC’s esp. cytostatic treatments, retinoids and photodynamic treatments. 4.Treatment with any systemic immunomodulating drugs or systemic retinoid 4 weeks prior to initial dosing. 5.Treatment with imiquimod 4 weeks prior to initial dosing. 6.Patients who are exposed to UV radiation an/or sun beds within 2 weeks before screening and during treatment. 7.Participation in any clinical investigation within 4 weeks prior to initial dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations. 8.A history of keloid scar development. 9.Donation or loss of 400 ml or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation. 10.Significant illness within two (2) weeks prior to initial dosing. 11.A past medical history of clinically significant ECG abnormalities. An abnormal ECG is defined as PR >220 msec, QRS complex >120 msec, QTcB> 440 msec females; QTcB> >430 msec males, or any significant morphological changes, other than non-specific T-wave changes. 12.History of multiple and recurring allergies or allergy to the investigational compound/compound class being used in this study. 13.Total WBC count which falls outside the range of 4500–11,000/µl, or platelets <100,000/µl at screening. 14.History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result. 15.A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. 16.History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening and/or at baseline.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Part II To determine: • The pharmacodynamic effect (histological signs of tumor regression and apoptosis) in BCC’s after treatment with topically applied 0.25% LDE225 cream and 0.75% LDE225 cream. • LDE225 pharmacokinetics in plasma after multiple applications of 0.25% LDE225 cream and 0.75% LDE225 cream onto the skin. ;Main Objective: Part II • To determine the safety and local tolerability of topically applied 0.25% LDE225 cream and 0.75% LDE225 cream on skin basal cell carcinomas (BCC’s) and perilesional uninvolved skin in Gorlin syndrome patients. • To assess the efficacy of topically applied 0.25% LDE225 cream and 0.75% LDE225 cream in treatment of multiple BCCs in Gorlin syndrome patients. ;Primary end point(s): See main objective section | — |
Countries
Austria
Outcome results
None listed