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Trial registered on ANZCTR


Registration number
ACTRN12616000272493
Ethics application status
Approved
Date submitted
22/02/2016
Date registered
1/03/2016
Date last updated
30/01/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Natural history and properties of naevi in advanced melanoma patients receiving treatment
Scientific title
A longitudinal, observational study investigating pigmentation genotypes and phenotypic correlations with dermoscopic naevus types and distribution in two participant groups; advanced stage melanoma patients undergoing targeted and/or immunotherapies, and a 'high risk' melanoma patient group.
Secondary ID [1] 288236 0
None
Universal Trial Number (UTN)
U1111-1178-0726
Trial acronym
None
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 297163 0
Condition category
Condition code
Skin 297382 297382 0 0
Other skin conditions
Cancer 297393 297393 0 0
Malignant melanoma
Human Genetics and Inherited Disorders 297394 297394 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Participants will undergo total body examination and mole count, including eye/hair/skin colour and density of freckling. In addition to total body photography, dermoscopic mole images will be captured using a digital dermoscope. We will require a saliva sample for genetic analysis. Study participants will be followed up every 4 months for one year (4 visits in total). If participants have any moles that are considered atypical by their dermatologist and therefore require excision, we would like to have residual tissue provided following clinical evaluation and diagnosis by the pathologist. this tissue sample would be used for further genetic analysis. During follow up visits, naevi which show clinical and dermoscopic changes in pigmentation are sampled using a microbiopsy device. DNA and RNA can be isolated from these samples for somatic genotyping. We will also take shave biopsies of other lesions (up to 3) for histopathology and genetic analysis.

Intervention code [1] 293530 0
Early Detection / Screening
Comparator / control treatment
Control group will consist of people considered high risk for melanoma (either by personal or family history, or by atypical mole syndrome), who are not currently undergoing any treatment for melanoma.
Control group
Active

Outcomes
Primary outcome [1] 296941 0
The primary outcome for the study is from the statistical analysis of the correlation of changing naevi pigmentation characteristics with genotyping and SNP typing of candidate genes in patients receiving treatment for advanced stage melanoma.

Naevi pigmentation characteristics are assessed using total body photography and individual dermoscopic images of naevi > 3mm.

Genotyping and SNP typing will be done by isolating DNA from saliva samples.
Timepoint [1] 296941 0
every 4 months for 1 year.
Primary outcome [2] 296942 0
Differences in somatic genotype/RNA expression profile of naevi that are characteristic of changeable naevi.

Analysis on somatic variations are possible by isolating DNA/RNA from individual naevi skin samples using either the microbiopsy or shave biopsy.
Timepoint [2] 296942 0
Every 4 months for 1 year
Secondary outcome [1] 321052 0
The secondary outcome for the study is from the statistical analysis of the correlation of changing naevi pigmentation characteristics with genotyping and SNP typing of candidate genes in a volunteer high risk cohort.

Naevi pigmentation characteristics are assessed using total body photography and individual dermoscopic images of naevi > 3mm.

Genotyping and SNP typing will be done by isolating DNA from saliva samples.
Timepoint [1] 321052 0
Every 4 months for 1 year

Eligibility
Key inclusion criteria
Cohort 1: melanoma patients with stage III and IV enrolled for treatment with targeted therapies and/or immunotherapies at the Cancer Services (PA Hospital). Baseline visit must be within 6 weeks of beginning melanoma treatment.

Cohort 2: participants considered high risk for melanoma under at least one of the following three subcategories;
a) Personal history of melanoma (stage I-IV, not in situ)
b) First degree family history of melanoma (stage I-IV, not in situ)
c) Atypical mole syndrome, defined as grater then 100 naevi, 6 (or more) atypical naevi (confirmed using dermoscopy), AND at least 1 naevus 8 mm (or greater) in dimension.

Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
All participants must be able to give informed consent.

All participants are asked to commit to 4 visits to the PA Hospital to participate in the trial over a 12 month period (months 0, 4, 8 and 12), as long as they are able to (Participants can withdraw from the study at any time for any reason).

Participants in cohort 2 must not be currently undergoing any treatment for melanoma.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
For the cross sectional data, descriptive statistical analyses including counts and proportions will be used to describe the number of naevi (> 3mm) and the average number of dysplastic naevi by participant sex, age and body site. Participants will be grouped by phenotype, or pigmentation/naevus genotype, and the number and type of naevi by body site in each of these subgroups will be summarised. Descriptive statistics will also be used to summarise dermoscopic features of naevi by body site. Depending on the distribution of the outcomes, parametric or non-parametric approaches to bivariate analyses will be considered.

To assess the unadjusted and adjusted strength of association between participants’ phenotypic or genotypic characteristics and naevi outcomes, linear or logistic regression models will be fitted, depending on whether the outcome is used in continuous or categorical format. These models will be conducted in crude and adjusted form to ascertain the independent contribution of explanatory factors (for example skin type) on the outcomes. Interaction terms will also be fitted where appropriate (for example phenotype and genotype) to explain naevus counts or distributions.

At each timepoint the cross sectional analyses will be repeated, and in addition changes in numbers of naevi over time will be calculated. Repeated measures models will be built to assess changes in naevus number, type or severity over time.

As this is an exploratory observational study, no formal sample size calculation was performed.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 5318 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 12780 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 292942 0
Government body
Name [1] 292942 0
National Health and Medical Research Council (NHMRC)
Address [1] 292942 0
GPO Box 1421, Canberra ACT 2601
Country [1] 292942 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
TRI, 37 Kent Street, Woolloongabba QLD 4102
Country
Australia
Secondary sponsor category [1] 291705 0
None
Name [1] 291705 0
none
Address [1] 291705 0
Country [1] 291705 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294446 0
Metro South Health HREC
Ethics committee address [1] 294446 0
TRI, Level 7, 37 Kent Street, Woolloongabba QLD 4102
Ethics committee country [1] 294446 0
Australia
Date submitted for ethics approval [1] 294446 0
14/01/2016
Approval date [1] 294446 0
29/03/2016
Ethics approval number [1] 294446 0
HREC/16/QPAH/037
Ethics committee name [2] 295005 0
University of Queensland HREC
Ethics committee address [2] 295005 0
The University of Queensland
St Lucia
Brisbane
Ethics committee country [2] 295005 0
Australia
Date submitted for ethics approval [2] 295005 0
29/03/2016
Approval date [2] 295005 0
07/04/2016
Ethics approval number [2] 295005 0
2016000429

Summary
Brief summary
This study aims to identify genetic differences and dermatological characteristics that pose greater risk for development of skin cancer.

Who is it for? You may be eligible to join this study if you are aged 18 years or more and are either undergoing targeted therapies and/or immunotherapies at the Cancer Services (PA Hospital) for stage III or IV melanoma OR if you are considered to be at a high risk of melanoma.

Study details: This is an observational prospective study (no additional treatment) on the natural history of naevi in advanced melanoma patients receiving treatment. This will include observations of molecular and genetic differences associated with changing naevi and melanoma risk. Patients will be followed up every 4 months for 1 year (4 visits in total) with 3D whole body photography and dermoscopy of all naevi larger than 3mm. The germline genotype is determined by collecting saliva together with baseline demographic data along with images. During follow up visits, naevi which show clinical and dermoscopic changes in pigmentation are sampled using a microbiopsy device. DNA and RNA can be isoalted from these samples for somatic genotyping. The same naevus can be sampled several times over the course of its growth and following visits. Additional shave biopsies (up to 3) will also be taken for comparative purposes. It is hoped that this study will lead to better understanding of genetic and phenotypic characteristics that lead to high risk of melanoma development and that may then assist in early diagnosis and preventative behaviours of skin cancer.
Trial website
www.naevi.centre.uq.edu.au

(not currently live)
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 62466 0
Prof H. Peter Soyer
Address 62466 0
Dermatology Research Centre, School of Medicine, The University of Queensland
TRI, 37 Kent Street, Woolloongabba QLD 4102
Country 62466 0
Australia
Phone 62466 0
61 7 3443 8017
Fax 62466 0
61 7 3443 7779
Email 62466 0
p.soyer@uq.edu.au
Contact person for public queries
Name 62467 0
Mrs Clare Primiero
Address 62467 0
Dermatology Research Centre, School of Medicine, The University of Queensland
TRI, 37 Kent Street, Woolloongabba QLD 4102
Country 62467 0
Australia
Phone 62467 0
61 7 3443 7496
Fax 62467 0
61 7 3443 7779
Email 62467 0
c.bover@uq.edu.au
Contact person for scientific queries
Name 62468 0
Mrs Clare Primiero
Address 62468 0
Dermatology Research Centre, School of Medicine, The University of Queensland
TRI, 37 Kent Street, Woolloongabba QLD 4102
Country 62468 0
Australia
Phone 62468 0
61 7 3443 7496
Fax 62468 0
61 7 3443 7779
Email 62468 0
c.bover@uq.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary