None listed
Conditions
Brief summary
One characteristic of Gorlin syndrome is that individuals typically develop numerous basal cell carcinomas over multiple areas of the body, with many occurring on the face and neck. The purpose of this study is to determine whether the drug Sonidegib is effective in reducing the size and number of tumours in patients with Gorlin syndrome. Who is it for? You may be eligible for this study if you are an adult who has been diagnosed with Gorlin syndrome (Basal Cell Nevus Syndrome). Study details All participants in this study will receive the study drug (Sonidegib), however participants will receive this drug for either 4, 6 or 8 weeks. The duration of treatment will be based upon enrolment which will occur by 1:1:1 allocation, into the three groups; 4 weeks, 6 weeks or 8 weeks of treatment. This means that you have a 1 in 3 chance of being in one these groups. All patients will receive treatment and standard practice of care. At each clinic visit your treating dermatologist will assess your skin and perform safety assessments (such as blood and urine samples). Participants will then be followed up for up to one year. During this time there are two phases. In the primary (first) treatment phase, you will be taking the study drug (Sonidegib) and a secondary phase where your lesions will be treated. During the secondary treatment phase, you will have 12 lesions treated; 3 lesions surgically excised, 3 lesions treated with cryosurgery and 3 lesions treated with topical Imiquimod cream. For lesions treated with topical Imiquimod cream, your study doctor will give you instructions on how to apply. It is hoped that this study will determine if Sonidegib can be used to decrease the excessive growth of tumours in patients with Gorlin Sydnrome.
Interventions
As a prospective intervention study, participants will be allocated into one of the three cohorts of varying treatment duration, in series. This means that Cohort 1 will be filled prior to Cohort 2 and so on.
Allocation into cohorts occurs at Week 0, where all cohorts will begin treatment for their allocated length of time (primary phase). At the end of the primary phase (4, 6 or 8 weeks), all participants will commence the secondary phase of treatment which involves the treatment of three le
As a prospective intervention study, participants will be allocated into one of the three cohorts of varying treatment duration, in series. This means that Cohort 1 will be filled prior to Cohort 2 and so on. Allocation into cohorts occurs at Week 0, where all cohorts will begin treatment for their allocated length of time (primary phase). At the end of the primary phase (4, 6 or 8 weeks), all participants will commence the secondary phase of treatment which involves the treatment of three lesions each (12 in total) with surgical excision, cryosurgery, topical Imiquimod (5%) cream and placebo cream. 1) Cohort 1: 4-week treatment with Sonidegib (Odomzo) 200 mg capsules (oral) once daily, 2) Cohort 2: 6-week treatment with Sonidegib (Odomzo) 200 mg capsules (oral) once daily 3) Cohort 3: 8-week treatment with Sonidegib (Odomzo) 200 mg capsules (oral) once daily. Participants are unable to participate in more than one cohort. Adherence/Accountability of study medication will involve returning of bottles of medication and counting of the remaining medication. The treating dermatologist will identify the 12 lesions that will undergo treatment (one of which will be surgical excision). The categorisation of each lesion to be treated with one of the four methods will be at their discretion. They will take into account location of the lesion, discomfort post treatment, standard care procedures etc. Standard care for both excisions and cryosurgery will be followed and performed by the treating dermatologist and relevant clinical staff to support if needed. The topical Imiquimod (5%) cream and placebo cream will be applied once daily, 5 days per week, for a period of 6 weeks. The creams will be administered by the patients using instructions and guidance provided by the treating dermatologist. Adherence for cream use will be monitored through the weight of the tubes at each visit. The amount of cream needed to cover the lesion will be used (e.g. surface area) and dosage to determine approximate grams of cream to be used per day/week etc.
Sponsors
Samson Clinical Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1) Males and females participants aged 18 years and above at Screening visit 2) Clinical diagnosis of Gorlin syndrome (Basal Cell Nevus Syndrome). Participants must satisfy the established criteria for diagnosis of Gorlin Syndrome 3) All target lesions (12 lesions) must be biopsied prior to successful enrolment into the study. 4) Participants must not require immediate surgical removal of lesions, or commence radiotherapy 5) No recent treatment for BCCs in the last 4 weeks prior to first dose of study medication 6) Female participants have to be either infertile (WONCBP), not pregnant, lactating, postmenopausal, surgically sterile or using acceptable and highly effective birth control methods. 7) Are willing to comply with all study requirements (primary and secondary treatment phases) including excision, cryotherapy and daily topical treatment of specific lesions. 8) Ability to comprehend and willing to sign and date an informed consent form (ICF).
Exclusion criteria
1) Have not met the Clinical diagnosis of Gorlin syndrome (Basal Cell Nevus Syndrome). Participants must satisfy the established criteria for diagnosis of Gorlin Syndrome. 2) Insufficient number of BCCs (minimum of 12 lesions) 3) Target tumor biopsy shows evidence of micronodular features, squamous metaplasia, sclerosing BCC, morpheic BCC, or peri-neural involvement 4) Participants receiving medications that are recognized to cause rhabdomyolysis or participants with a prior history of rhabdomyolysis 5) previous use of topical treatment to treat BCCs in the 4 weeks prior to first dose of study drug 6) previous 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 7) Participants requiring immediate surgical removal of lesions or other related emergency interventions 8) Immunocompromised (e.g. known Hepatitis B or C infection, HIV infection) or is receiving or is expected to receive an immunomodulating agent (including immunosuppressive agents, cytotoxic drugs, biological agents, immunoglobulins, interferon or other immune or cytokine-based therapies. 9) Eastern Cooperative Oncology Group (ECOG) performance status > 1. 10) Known or suspected metastatic disease. 11) Clinically active or uncontrolled skin disease that would interfere with evaluation of the area surrounding the target tumour (e.g. eczema, unstable psoriasis) 12) Any experimental or investigational agents within 6 weeks of first dose of study drug 13) Female participants who are pregnant, planning a pregnancy or nursing a child or not on an acceptable and highly effective birth control method. 14) Female participants who are of child-bearing potential (WOCBP) who are not on 2 methods of contraception (1 highly effective method and 1 barrier method) 15) Any clinically significant abnormal laboratory values as determined by the Principal Investigator. 16) Unwilling to comply with all study procedures and assessments
Outcome results
None listed