Please be advised that due to the high volume of submissions, the ANZCTR is currently experiencing delays in processing submissions from those outside of Australia and New Zealand. As the ANZCTR is funded by Australia and New Zealand, we must prioritise submissions from these countries first. International submissions should allow additional time for registration. Apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12619001044112
Ethics application status
Approved
Date submitted
25/06/2019
Date registered
23/07/2019
Date last updated
23/07/2019
Date data sharing statement initially provided
23/07/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Autoantibody Biomarkers for Melanoma Detection.
Scientific title
Evaluation of the Diagnostic Accuracy of a Multiplex Test for the Early Diagnosis of Melanoma
Secondary ID [1] 298526 0
Tour de Cure 17-ECOW-RS-01
Universal Trial Number (UTN)
n/a
Trial acronym
MelDx
Linked study record
This is the parent study of the proposed project. The trial will evaluate the diagnostic accuracy of the biological signature identified in the record below:
Zaenker P, Lo J, Pearce R, Cantwell P, Cowell L, Lee M, Quirk C, Law H, Gray E, Ziman M. A diagnostic autoantibody signature for primary cutaneous melanoma. Oncotarget. 2018 Jul 17;9(55):30539-30551. doi: 10.18632/oncotarget.25669. PubMed PMID: 30093967; PubMed Central PMCID: PMC6078131.

Health condition
Health condition(s) or problem(s) studied:
Melanoma 313336 0
Condition category
Condition code
Cancer 311777 311777 0 0
Malignant melanoma

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The MelDx blood test aims to identify a combination of autoantibodies (including ZBTB7B, PRKCH, TP53, PCTK1, PQBP1, UBE2V1, IRF4, MAPK8_tv2, MSN and TPM1 and potentially other refined combinations of these or new antibodies) in the blood of patients with suspicious lesions thought be be a melanoma.

This is a prospective trial aimed to confirm the efficacy, sensitivity and specificity of the melanoma diagnostic test, MelDx, in collaboration with GPs, Skin Check specialists, dermatologists and plastic surgeons.

In this trial,
• blood will be collected from 1000 participants with suspected melanoma via routine venepuncture prior to the collection of the routine biopsy of the lesion for diagnosis.
• The result of the blood test will be compared with that from the biopsy and statistical analyses of the diagnostic accuracy of the MelDx test will be determined.

We propose that a blood test based on a diagnostic autoantibody signature (as described in Zaenker et al. 2018) from patient sera can be used in conjunction with current melanoma diagnostic techniques, to improve the early diagnosis and diagnostic certainty of melanoma to ultimately decrease the mortality rate of patients.

Hypothesis

Autoantibody positivity in sera using the MelDx test will correspond with histological diagnosis of melanoma via biopsy.

Primary Aim
To validate a combination of autoantibodies that provide diagnostic accuracy of 80% or greater in early stage melanoma.

Secondary Aim
To evaluate whether a history of skin cancers affects the test results.
To evaluate the specificity of MelDx for melanoma relative to other skin cancers, other cancers and autoimmune diseases.
Intervention code [1] 314776 0
Diagnosis / Prognosis
Intervention code [2] 315059 0
Early Detection / Screening
Comparator / control treatment
Participants will undergo skin checks as usual, Where a suspicious lesion is identified by a collaborating clinician, the participant will be asked to provide a blood sample prior to the collection of standard care biopsies. The blood will be screening against the MelDx test and results will be compared to biopsy results.
Control group
Active

Outcomes
Primary outcome [1] 320462 0
Evaluation of the diagnostic accuracy of a combination of autoantibodies as assessed by comparison of the MelDx blood test to gold standard skin biopsy for early melanoma detection.

Timepoint [1] 320462 0
Participant blood is collected prior to the collection of the biopsy of a suspicious lesion. Every participant will provide a blood sample only once.
Sample collection will continue until a sufficient number of samples has been collected (at least 100 confirmed melanoma cases are required which may necessitate the collection of approx. 1000 samples). Once all samples have been collected, these will be tested against the MelDx blood test and the results will reveal the overall diagnostic accuracy of the test relative to the standard biopsy.
Secondary outcome [1] 371678 0
To evaluate whether a history of skin cancers affects the test results. Individual participant notes on skin cancer history will be documented by the principal researchers and collaborating clinicians. All associated pathology reports will be collected were available. The results (antibody levels) of participants with a history of non-melanoma skin cancer will be compared directly to the results of participant with no prior history of other skin cancers.
Timepoint [1] 371678 0
upon study completion, these samples will be tested at the same timepoint as the primary outcome of the trial
Secondary outcome [2] 371679 0
To evaluate the specificity of MelDx for melanoma.
To confirm that our test is indeed melanoma specific we will include an additional set of control samples from patients with confounding diseases; non-melanoma skin cancers, prostate, colon or breast cancer, as well as autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematodes (SLE) or multiple sclerosis (MS).
Timepoint [2] 371679 0
upon study completion, these samples will be tested at the same timepoint as the primary outcome of the trial

Eligibility
Key inclusion criteria
Subject Population
The study population will be drawn from WAKMAS, private and public practices and hospitals. The patients will provide a blood sample prior to the time of biopsy for an early stage cutaneous melanoma.

Inclusion Criteria:
• Participants who have an abnormal skin lesion thought to be melanoma or other non-melanoma skin cancers or participants who have recently been diagnosed with other types of primary cancer or an autoimmune disease
• >18 years
• Written informed consent
• Willing and able to comply with study blood collection protocol
• Willing to provide relevant biopsy pathology report


Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria:
• People previously diagnosed with metastatic melanoma (TNM stage III and IV)
• Previously diagnosed with other cancers (excluding skin cancers)
• Surgical procedure in the last three months
• Previously diagnosed with an autoimmune disease

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
The proposed research activity will include the recruitment and consenting of study participants. Over 1000 participants will be recruited by the collaborating clinicians (assuming that 10% will be melanoma cases). Based on a statistical analysis of an Area Under the Curve (AUC) of 0.663 for our most sensitive marker in our previous analyses, we calculated that the sample size required for an alpha of 0.05 and 95% power is a minimum of 76 cases in each group (TNM stage 0-II melanoma and age and gender matched healthy volunteers) but will recruit at least 100 cases. Each participant will be asked to provide a blood sample that will be collected by a trained phlebotomist via routine venepuncture prior to the collection of their routine skin biopsy. A small subset of participants may be asked to provide another blood sample 12 months after their initial sample donation.
Blood samples will be screened on a human protein microarray for validation of the identified autoantibodies and to identify new novel autoantibodies (CDI array, USA).
After that, a multiplex Luminex protein bead-based assay will be designed from the best set of autoantibodies identified on the array and once developed will be used to validate the multiplex autoantibody test for melanoma. This Luminex test will be developed in collaboration with national and international collaborators. Once developed, the test will be used with over 1000 blood samples to validate the multiplex autoantibody blood test for its efficacy to differentiate very early stage melanoma patients from healthy volunteers. To ascertain the test sensitivity, samples from other cancer types as well as autoimmune diseases will be tested.

Recruitment
Recruitment status
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)
WA

Funding & Sponsors
Funding source category [1] 303046 0
Charities/Societies/Foundations
Name [1] 303046 0
Tour de Cure
Address [1] 303046 0
Suite 2, Level 1, Building B
14 Rodborough Road
Frenchs Forest, NSW, 2086
Country [1] 303046 0
Australia
Primary sponsor type
University
Name
Edith Cowan university
Address
270 Joondalup Drive
Joondalup, WA. 6027
Country
Australia
Secondary sponsor category [1] 303057 0
None
Name [1] 303057 0
Address [1] 303057 0
Country [1] 303057 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303596 0
Edith Cowan University Human Research Ethics Committee
Ethics committee address [1] 303596 0
270 Joondalup Drive
Joondalup, WA, 6027
Ethics committee country [1] 303596 0
Australia
Date submitted for ethics approval [1] 303596 0
Approval date [1] 303596 0
14/05/2018
Ethics approval number [1] 303596 0
18957

Summary
Brief summary
This study aims to develop a multi-marker assay that will serve as a diagnostic blood test for the detection of early stage melanoma skin cancer (cutaneous melanoma).

Who is it for?
You may be eligible to join this study if you are aged 18 years or older and have an abnormal skin lesion thought to be melanoma or other types on non-melanoma skin cancer. You must be willing to provide a blood sample prior to your routine skin biopsy. You may additionally be able to participate if you have recently been diagnosed with other types of cancer (early stages) or an autoimmune disease.

Study details
This study will involve taking a blood sample with a needle from your arm prior to the routine biopsy of your skin lesion. This blood sample will be tested for specific antibodies related to melanoma. The results of this blood test will be compared to results of the biopsy in order to determine how accurate it is at detecting melanoma.

It is hoped that this blood test can be used to provide greater diagnostic certainty prior to biopsy and for routine screening of people who are at a higher risk of melanoma.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94202 0
Dr Pauline Zaenker
Address 94202 0
Edith Cowan University
Building 17 Level 2 PO BOX 2
270 Joondalup Drive
Joondalup, WA, 6027
Country 94202 0
Australia
Phone 94202 0
+61 8 6304 2783
Fax 94202 0
Email 94202 0
p.zaenker@ecu.edu.au
Contact person for public queries
Name 94203 0
Dr Pauline Zaenker
Address 94203 0
Edith Cowan University
Building 17 Level 2 PO BOX 2
270 Joondalup Drive
Joondalup, WA, 6027
Country 94203 0
Australia
Phone 94203 0
+61 8 6304 2783
Fax 94203 0
Email 94203 0
p.zaenker@ecu.edu.au
Contact person for scientific queries
Name 94204 0
Dr Pauline Zaenker
Address 94204 0
Edith Cowan University
Building 17 Level 2 PO BOX 2
270 Joondalup Drive
Joondalup, WA, 6027
Country 94204 0
Australia
Phone 94204 0
+61 8 6304 2783
Fax 94204 0
Email 94204 0
p.zaenker@ecu.edu.au

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?
Informed consent form
How or where can supporting documents be obtained?
Type [1] 2375 0
Informed consent form
Citation [1] 2375 0
Link [1] 2375 0
Email [1] 2375 0
Other [1] 2375 0
Summary results
No Results