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Trial registered on ANZCTR


Registration number
ACTRN12620001200976
Ethics application status
Approved
Date submitted
10/08/2020
Date registered
12/11/2020
Date last updated
12/11/2020
Date data sharing statement initially provided
12/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Sonidegib (Odomzo) neo-adjuvant therapy for participants with Gorlin syndrome – A pilot study
Scientific title
Sonidegib (Odomzo) neo-adjuvant therapy for participants with Gorlin syndrome – A pilot study
Secondary ID [1] 299478 0
ODOMG001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gorlin Syndrome 314820 0
Condition category
Condition code
Cancer 313161 313161 0 0
Other cancer types
Skin 313162 313162 0 0
Other skin conditions
Human Genetics and Inherited Disorders 316962 316962 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 315811 0
Treatment: Drugs
Intervention code [2] 315812 0
Treatment: Surgery
Comparator / control treatment
Comparator treatment is the treatment of lesions with Sonidegib with placebo cream, which will be evaluated against traditional therapies of surgical excision, cryosurgery or topical Imiquimod cream.
Control group
Active

Outcomes
Primary outcome [1] 321687 0
Assessment of pre-determined tumours (taking into account the presence of any shrinkage) in patients, as reviewed and documented by dermatologist and assessed by Global Clinical Assessment and full body photography (incl. dermatoscopic imaging of target lesions)

Characteristics of the tumours will be assessed by Global Clinical Assessment and usual standard practice.
The Global Clinical Assessment will use the following criteria:
0= No change
1= < 50% decrease in lesion
2= 50-90% decrease in lesion
3= 91-99% decrease in lesion
4= complete disappearance of lesion.
The number of recurrent BCCs will be compared between each primary treatment group and each secondary treatment modality.
Timepoint [1] 321687 0
The primary timepoint is Week 4 (cohort 1), 6 (cohort 2) or 8 (cohort 3).
Primary outcome [2] 321688 0
Assessment of tumours and changes through measurement of lesions, as reviewed and documented by investigator and assessed by Global Clinical Assessment and full body photography (incl. dermatoscopic imaging of target lesions).

Characteristics of the tumours will be assessed by Global Clinical Assessment and usual standard practice.
The Global Clinical Assessment will use the following criteria:
0= No change
1= < 50% decrease in lesion
2= 50-90% decrease in lesion
3= 91-99% decrease in lesion
4= complete disappearance of lesion.
The number of recurrent BCCs will be compared between each primary treatment group and each secondary treatment modality.
Timepoint [2] 321688 0
After cryotherapy of lesions (n=3) at week 4 (cohort 1), 6 (cohort 2), 8 (cohort 3), and topical treatments (Imiquimod or placebo) at timepoints; week 10 (cohort 1), 12 (cohort 2) or 14 (cohort 3); and at the end of the study (Week 52 for all cohorts)."
Secondary outcome [1] 375896 0
Ease of excision of lesions (n=3) following treatment as assessed by dermatologist according to usual standard practice.

(e.g. potential conversion of a difficult to resect laBCC into a more easily resectable BCC as per the judgement and discretion of the treating dermatologist).
Timepoint [1] 375896 0
The secondary timepoint is at the end of the primary phase, at 4 (cohort 1), 6 (cohort 2) or 8 weeks (cohort 3).
Secondary outcome [2] 375897 0
Ease of removal of lesions (n=3, refractory BCC) by cryotherapy (n=3) and topical treatment (Imiquimod, n=3, or placebo n=3) as assessed by dermatologist and following usual standard practice.
Timepoint [2] 375897 0
The secondary timepoint is in 52 weeks for all cohorts.
Secondary outcome [3] 386759 0
Safety and tolerability will be assessed against currently known side-effects profile for long-term treatment with Odomzo (greater or equal to 12 weeks) by patient reported and trained investigator assessment. Additionally, personal medical records (e.g. hospital records) may be consulted in the unlikely chance of a linked serious adverse event.
Timepoint [3] 386759 0
Short term treatment-emergent side effects/adverse events will be assessed at 4 weeks (cohort 1), 6 weeks (cohort 2) and 8 weeks (cohort 3).

Eligibility
Key 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).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
As a non-randomised trial, 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).
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
N/A. No power calculations were performed as this is a pilot study.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/11/2020
Actual
Date of last participant enrolment
Anticipated
31/03/2021
Actual
Date of last data collection
Anticipated
30/06/2021
Actual
Sample size
Target
6
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 14965 0
Sinclair Dermatology - East Melbourne
Recruitment postcode(s) [1] 28251 0
3002 - East Melbourne

Funding & Sponsors
Funding source category [1] 303978 0
Other
Name [1] 303978 0
Samson Clinical Pty Ltd
Country [1] 303978 0
Australia
Primary sponsor type
Other
Name
Samson Clinical Pty Ltd
Address
2 Wellington Parade
East Melbourne VIC 3002
Country
Australia
Secondary sponsor category [1] 304150 0
None
Name [1] 304150 0
NA
Address [1] 304150 0
NA
Country [1] 304150 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304477 0
Bellberry Limited
Ethics committee address [1] 304477 0
123 Glen Osmond Road
Eastwood SA 5063
Ethics committee country [1] 304477 0
Australia
Date submitted for ethics approval [1] 304477 0
02/09/2018
Approval date [1] 304477 0
18/12/2018
Ethics approval number [1] 304477 0
2018-08-643

Summary
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.
Trial website
NA
Trial related presentations / publications
NA
Public notes

Contacts
Principal investigator
Name 97086 0
Prof Rodney Sinclair
Address 97086 0
Sinclair Dermatology
Level 2, 2 Wellington Parade
East Melbourne VIC 3002
Country 97086 0
Australia
Phone 97086 0
+61 03 9013 0099
Fax 97086 0
Email 97086 0
[email protected]
Contact person for public queries
Name 97087 0
Jennifer Kieran
Address 97087 0
Sinclair Dermatology
Level 2, 2 Wellington Parade
East Melbourne VIC 3002
Country 97087 0
Australia
Phone 97087 0
+61 03 96542426
Fax 97087 0
Email 97087 0
[email protected]
Contact person for scientific queries
Name 97088 0
Laita Bokhari
Address 97088 0
Sinclair Dermatology
Level 2, 2 Wellington Parade
East Melbourne VIC 3002
Country 97088 0
Australia
Phone 97088 0
+61 03 9013 0099
Fax 97088 0
Email 97088 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.