Patients with germline CYLD mutations (OMIM 605018). These include Brooke-Spiegler Syndrome, familial cylindromatosis and multiple familial trichoepitheliomas (OMIM #605041, #132700, #601606 respectively).
Conditions
Interventions
Product Name: CT327
Product Code: CT327
Pharmaceutical Form: Ointment
INN or Proposed INN: CT327
Concentration unit: % (W/W) percent wei
Sponsors
Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cohort 1: •Males and females age 18 years and older •Patients from genotyped pedigrees with known CYLD mutations; or if they have a clinical phenotype compatible with this diagnosis •Patients that are suitable for the trial will have at least one eligible tumour •The eligible tumour will be scheduled for removal >4 weeks from consent •The eligible tumour must be no more than 3cm in size •For women of childbearing age: a negative pregnancy test is required prior to study entry, and on completion of trial treatment. The patient must be using an adequate contraception method and agree to continue using this throughout the trial and for at least 2 weeks after stopping trial medication •Sexually active men must agree to use barrier forms of contraception •The recruiting clinician must be confident that the patient understands the consent process and has the capacity and willingness to provide fully informed consent for participation in the trial Cohort 2: •Males and females age 18 years and older •For women of child bearing age: a negative pregnancy test is required prior to study entry, and on completion of trial treatment. The patient must be using an adequate contraception method and agree to continue using this throughout the trial and for at least 2 weeks after stopping trial medication •Patients from genotyped pedigrees with known CYLD mutations, or if they have a clinical phenotype compatible with this diagnosis •Patients will optimally have 8-10 eligible tumours •Eligible tumours will be less than 1 cm in diameter and no more than 2 cm in diameter at the base •Eligible tumours must be spaced at least 1 cm apart from other eligible tumours to avoid cross-contamination •The recruiting clinician must be confident that the patient understands the consent process and has the capacity and willingness to provide fully informed consent for participation in the trial •Patients who have completed Phase 1b without adverse reaction and after completing a minimum 2 week treatment free washout period Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: Cohort 1: •Patients aged 2cm base diameter will not be eligible •Any tumour within 10cm of an excision scar of a cohort 1treated site will not be eligible •Use of any other topically administered treatments at the treatment site
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: In Cohort 1 the timepoint of evaluation is at 4 weeks. In Cohort 2 the timepoints of evaluation are at 4 weeks and 12 weeks.;Main Objective: The principal research objective for Cohort 1 is to find out whether CT327 (an ointment with a drug called a TRK inhibitor in it) is a safe treatment for patients with CYLD defective tumours (lumps). The principal research objective for Cohort 2 is to investigate whether CYLD defective tumours (lumps) respond to CT327.;Secondary Objective: Secondary objectives for Cohort 1 are to measure quality of life (questionnaire), skin and tumour (lump) appearance and patient treatment compliance (patient diary). Secondary objectives for Cohort 2 are to establish the way that the study drug works on the size of CYLD defective tumours (lumps) using genetic techniques and protein measurement.;Primary end point(s): The primary outcome measure for Cohort 1 is the number of patients with severe treated skin site reactions as determined by Modified Draize score, after a 4 week treatment period. The primary outcome measure for Cohort 2 is the proportion of tumours responding to treatment by 12 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): In Cohort 1 the secondary endpoints are; Impact of disease on quality of life, acceptability of treatment, and concentration of CT327 in plasma. In Cohort 2 the secondary endpoints are; the number of adverse events within a planned 12 week treatment period, expression of targets of TRK signalling in tumour biopsies as determined by QPCR and immunohistochemistry, concentration of CT327 in plasma and a proportion of tissue samples. ; Timepoint(s) of evaluation of this end point: The timepoint of evaluation in cohort 1 is at 4 weeks. The timepoints of evaluation in cohort 2 is at 4 weeks and 12 weeks. | — |
Countries
United Kingdom
Contacts
Public ContactNeil Rajan
Newcastle University
Outcome results
None listed