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Trial registered on ANZCTR


Registration number
ACTRN12621001715864p
Ethics application status
Submitted, not yet approved
Date submitted
20/10/2021
Date registered
15/12/2021
Date last updated
15/12/2021
Date data sharing statement initially provided
15/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Trial of sirolimus cream in organ transplant recipients to prevent skin cancer.
Scientific title
A randomised double-blind placebo-controlled trial of topical sirolimus in chemoprevention of facial squamous cell carcinomas in solid organ transplant recipients
Secondary ID [1] 293329 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record
This study is a follow-up phase III randomised double blinded control trail to registration record ACTRN12618001961235 which was a phase II randomised double blinded control trial. However, it studying the topical 1% sirolimus being applied in a cream formulation in a different area of the body.

Health condition
Health condition(s) or problem(s) studied:
Squamous cell carcinoma 323682 0
Basal cell carcinoma 323683 0
Keratinocyte cancer 323684 0
Condition category
Condition code
Cancer 321219 321219 0 0
Non melanoma skin cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Sirolimus 1% cream (in a vehicle) or placebo (vehicle only) will be applied by the participant nightly for six months onto the participants face. This is a double blinded randomised control trial, therefore the participants will not know if they are applying the intervention or placebo. The creams will be applied in a thin layer only, and will be delivered in a pump container to enable standardised delivery of intervention/placebo. The number of successful applications of the cream are assessed by participants completing a daily record of application. In addition, they are provided the cream in two consecutive 3 month containers which will be returned at three and six months respectively. This enables researchers to monitor adherence through assessing the number of applications on their recording sheet and the amount of product left at three months. Participants will also be reminded to apply the cream through phone calls/messages.
Intervention code [1] 321759 0
Treatment: Drugs
Comparator / control treatment
The placebo contains the vehicle only cream. The placebo will be applied by the participant nightly for six months onto the participants face. This is a double blinded randomised control trial, therefore the participants will not know if they are applying the intervention or placebo.

The placebo/vehicle contains mucopolysaccharide polysulphate (MPS) cream mixing Deionised water, Propylene Glycol, Caprylic/Capric Triglyceride, Laureth-7, Potassium Sorbate, Phenoxyethanol, Benzyl Alcohol, Aloe Barbadensis leaf Juice, Polyacrylamide, C 13-14 Isoparaffin, Tocopheryl Acetate.
Control group
Placebo

Outcomes
Primary outcome [1] 329004 0
The primary outcome measure is the number of biopsy proven squamous cell carcinomas present at each time-point, as compared to initiation day.
Timepoint [1] 329004 0
6 months, 12 months (primary timepoint) and 24 months post commencement of applying topical sirolimus/placebo.
Secondary outcome [1] 401135 0
The occurrence of intraepidermal carcinomas at each of the time-points, assessed via biopsy results or visual inspection by specialist.
Timepoint [1] 401135 0
6 months, 12 months and 24 months post commencement of applying topical sirolimus/placebo.
Secondary outcome [2] 401136 0
The number of actinic keratoses of each patient at recruitment compared to the end of the study on photographic images and counts.
Timepoint [2] 401136 0
Baseline and 6 months post commencement of applying topical sirolimus/placebo.
Secondary outcome [3] 401137 0
The feasibility of applying topical sirolimus every night to the face for 6 months. This is assessed through participants filling out a recording sheet to reflect the number of applications successfully done. In addition, a questionnaire specifically made for this trial will also be filled out by participants to gauge their willingness to apply this cream every night for a prolonged period of time.
Timepoint [3] 401137 0
Three and six months post commencement of applying topical sirolimus/placebo.
Secondary outcome [4] 401138 0
The occurrence and type of intervention-related side effects - such as skin dryness or irritation or folliculitis. This is assessed at an in person review halfway through applying the cream (i.e. at three months) and through participants filling out a recording sheet at home if they had any side effects. Participants will also be contacted monthly either via email, phone call or text message ask about any possible side effects. Medical records will be monitored during and post applying of the cream to monitor for any further side effects or non trial related medical problems.
Timepoint [4] 401138 0
Baseline and then monthly until completion of applying the cream, and then 6 months, 12 months and 24 months post completion of applying topical sirolimus/placebo.
Secondary outcome [5] 401139 0
The number of doses applied during the six months by participants. This is assessed through participants filling out a recording sheet for every application applied.
Timepoint [5] 401139 0
At the completion of applying topical sirolimus/placebo for six months.
Secondary outcome [6] 401140 0
Participant satisfaction on applying regular topical sirolimus. This will be assessed through a questionnaire specifically designed for this study, EuroQol five-dimensional (EQ-5D-5L) questionnaire and the Basal and Squamous Cell Carcinoma QoL (BaSQoL) questionnaire.
Timepoint [6] 401140 0
Three months and six months post commencement of applying topical sirolimus.
Secondary outcome [7] 402908 0
The occurrence of basal cell carcinomas at each of the time-points. This will be assessed via biopsy results.
Timepoint [7] 402908 0
6 months, 12 months and 24 months post commencement of applying topical sirolimus/placebo.
Secondary outcome [8] 402909 0
The occurrence of subtypes of basal cell carcinomas at each of the time-points. This will be assessed via biopsy results.
Timepoint [8] 402909 0
6 months, 12 months and 24 months post commencement of applying topical sirolimus/placebo.
Secondary outcome [9] 402910 0
The occurrence of subtypes of squamous cell carcinomas at each of the time-points. This will be assessed via biopsy results.
Timepoint [9] 402910 0
6 months, 12 months and 24 months post commencement of applying topical sirolimus/placebo.
Secondary outcome [10] 402911 0
The number of patients completing the six month course. This is assessed both verbally and through participants filling out a recording sheet for every application applied.
Timepoint [10] 402911 0
At the completion of applying topical sirolimus/placebo for six months.
Secondary outcome [11] 402913 0
To determine the cost-effectiveness of using topical sirolimus therapy in comparison to the current standard of care, being surgical intervention, in the management of KCs. This will be assessed through EuroQol five-dimensional (EQ-5D-5L) questionnaire and the Basal and Squamous Cell Carcinoma QoL (BaSQoL) questionnaire.
Timepoint [11] 402913 0
3 months, 6 months, 12 months and 24 months post commencement of applying topical sirolimus/placebo.

Eligibility
Key inclusion criteria
Be aged 18 years or older
Have received an organ transplant 12 months ago or earlier
Have had least 1 SCC/BCC in the past 5 years
Have at least 5 keratotic lesions on their face at inclusion
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Are unable to provide informed consent
Are currently receiving sirolimus or everolimus orally
Have a skin cancer on their face requiring treatment
Have an open wound on their face requiring treatment
Are pregnant or planning to become pregnant in the next 6 months
Are medically unstable
Have difficulty understanding and signing the PICF document (are non-English speaking or intellectually impaired)
Non-english speaking patients

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Assuming that the IECs detected at 6 months in our preliminary study will become invasive at a later stage, we used the average number of IECs per patient to inform the sample size calculation of this trial. Based on that pilot data, in which 12 IECs were diagnosed in 29 placebo arms in 2 years and 4 IECs were detected in 29 sirolimus arms in the same time period, we assume that the underlying diagnosis rates in the placebo and sirolimus arms are 0.414 and 0.138 SCC/patient respectively over 2 years. To achieve power of 80% with a two-sided Type I error rate of 0.05, 47 patients are required to be tested in each arm with a 1:1 enrolment ratio between arms. Factoring in the expected high level of trial dropouts (36%), we will aim to recruit a minimum of 73 patients per arm totalling 146 patients.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
31/01/2022
Actual
Date of last participant enrolment
Anticipated
31/07/2022
Actual
Date of last data collection
Anticipated
31/07/2024
Actual
Sample size
Target
146
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 20553 0
The Prince Charles Hospital - Chermside
Recruitment hospital [2] 20554 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 35335 0
4032 - Chermside
Recruitment postcode(s) [2] 35336 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 297953 0
Government body
Name [1] 297953 0
Metro South Health (Metro South Health Research Support Scheme / Metro South Health Study, Education and Research Trust Account)
Country [1] 297953 0
Australia
Primary sponsor type
University
Name
University of Queensland
Address
University of Queensland Diamantina Institute
Level 6, Translational Research Institute
37 Kent Street, Woolloongabba QLD 4102
Country
Australia
Secondary sponsor category [1] 311527 0
None
Name [1] 311527 0
none
Address [1] 311527 0
.
Country [1] 311527 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 298995 0
Metro South HREC
Ethics committee address [1] 298995 0
Ethics committee country [1] 298995 0
Australia
Date submitted for ethics approval [1] 298995 0
19/08/2021
Approval date [1] 298995 0
Ethics approval number [1] 298995 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78934 0
Prof Kiarash Khosrotehrani
Address 78934 0
University of Queensland Diamantina Institute
Translational Research Institute
Level 6
37 Kent Street
Woolloongabba QLD 4102
Country 78934 0
Australia
Phone 78934 0
+61 734437088
Fax 78934 0
+61 734436966
Email 78934 0
k.khosrotehrani@uq.edu.au
Contact person for public queries
Name 78935 0
Charlotte Cox
Address 78935 0
University of Queensland Diamantina Institute
Translational Research Institute
Level 6
37 Kent Street
Woolloongabba QLD 4102
Country 78935 0
Australia
Phone 78935 0
+61486030731
Fax 78935 0
Email 78935 0
charlotte.cox1@uqconnect.edu.au
Contact person for scientific queries
Name 78936 0
Kiarash Khosrotehrani
Address 78936 0
University of Queensland Diamantina Institute
Translational Research Institute
Level 6
37 Kent Street
Woolloongabba QLD 4102
Country 78936 0
Australia
Phone 78936 0
+61 734437088
Fax 78936 0
+61 734436966
Email 78936 0
k.khosrotehrani@uq.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data underlying published results, only after de-identification.
When will data be available (start and end dates)?
Immediately following publication, no end date determined
Available to whom?
Case-by-case basis at the discretion of Primary Sponsor
Available for what types of analyses?
Only to achieve the aims in the approved proposal
How or where can data be obtained?
Access subject to approvals by Principal Investigator - Professor Kiarash Khosrotehrani, UQ Diamantina Institute, +61 7 344 37088


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
13273Study protocol.   373969-(Uploaded-13-10-2021-22-07-18)-Study-related document.pdf
13274Informed consent form.   373969-(Uploaded-12-11-2021-15-33-00)-Study-related document.pdf



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.