Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000487718p
Ethics application status
Submitted, not yet approved
Date submitted
16/03/2022
Date registered
28/03/2022
Date last updated
28/03/2022
Date data sharing statement initially provided
28/03/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the effect of Metabolomics on Responses to ImmunoTherapy - in Melanoma
Scientific title
Metabolomics in Ehancing Responses to ImmunoTherapy - in adult Melanoma patients
Secondary ID [1] 306280 0
None known
Universal Trial Number (UTN)
U1111-1273-6819
Trial acronym
MERIT-M
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 325057 0
Condition category
Condition code
Cancer 322493 322493 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
Patients with resected and unresectable melanoma who are undergoing checkpoint inhibitor therapy will undergo blood and faecal metabolomic profiling in order to identify the metabolites associated with successful immunotherapy responses. We will collect one tube of blood and one faecal sample at three time points during checkpoint inhibitor treatment. This includes baseline, week 6 and at 6 months or development of disease progression. The blood draw will take 10 minutes and the faecal collection will be conducted at home.

Patient data will be followed up for a total of 24 months post enrollment - this will be based on medical records.
Intervention code [1] 322728 0
Early Detection / Screening
Comparator / control treatment
Patients will be divided into groups including Responder and Non-Responder based on response to checkpoint inhibitor therapy. Patients with good responses to immunotherapy (based on RECIST 1.1 criteria) will be compared to those with poor responses.
Control group
Active

Outcomes
Primary outcome [1] 330280 0
Metabolomics analysis will be performed on blood including (i) a targeted assay that quantifies 9 SCFA, and (ii) untargeted metabolomics for unbiased metabolomics signature.
Timepoint [1] 330280 0
Samples wil be collected at enrollment, at 6 weeks and then either at disease progression or at the 6 month mark - whichever comes first.
Primary outcome [2] 330858 0
Metabolomics analysis will be performed on faeces including (i) a targeted assay that quantifies 9 SCFA, and (ii) untargeted metabolomics for unbiased metabolomics signature.
Timepoint [2] 330858 0
Samples wil be collected at enrollment, at 6 weeks and then either at disease progression or at the 6 month mark - whichever comes first.
Secondary outcome [1] 405553 0
Disease free survival as assessed by reviewing patient imaging. Disease free survival is defined as the length of time that the patient has scans that show absence of melanoma.
Timepoint [1] 405553 0
Overall survival at 2 years

Eligibility
Key inclusion criteria
Patients with resected and unresectable melanoma who are undergoing checkpoint inhibitor therapy.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with active, untreated brain metastases
Patients on > 10mg prednisone at baseline
Active autoimmune disease (excludes vitiligo, treated thyroid disease, diabetes)
Crohn’s disease or ulcerative colitis
The presence of any other neoplasm in the past 5 years – deemed ‘not under control’
Pregnancy
Inability to give informed consent
HIV
Hepatitis B or C
Prior treatment with immunotherapy – if patient had adjuvant immunotherapy – date of relapse must have been > = 6 months prior to study entry
Active mental illness that prohibits study entry
Radiotherapy within previous 4 weeks except to brain mets
Concurrent use of any other investigational or experimental product or therapeutic

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
To assess feasibility of this study, first we will compare expression levels of the several known metabolites between NR and R patients using t-tests on log-transformed expression levels with FDR adjustment. Secondly a non-targeted comparison of 100 metabolites will seek to identify other biomarkers that may differ between NR and R with similar magnitude as the a-priori identified markers. Log fold-change from baseline will be analysed for each subsequent time-point using the same approach as above. To explore whether there are metabolomics profiles comprising multiple markers that differentiate NR vs R patients we will use penalised logistic regression (eg Lasso), and tree-based machine learning methods (eg boosted tree) to identify sets of markers that together predict response. We will tune these models using leave-one-out cross validation to maximise the utility of the small sample size. We may also perform correlation and cluster analyses on the set of biomarkers to develop an understanding of which markers tend to co-occur in patients.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/06/2022
Actual
Date of last participant enrolment
Anticipated
1/02/2024
Actual
Date of last data collection
Anticipated
1/06/2024
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 21572 0
The Wesley Hospital - Auchenflower
Recruitment postcode(s) [1] 36492 0
4066 - Auchenflower

Funding & Sponsors
Funding source category [1] 310628 0
Charities/Societies/Foundations
Name [1] 310628 0
Uniting Care Health
Country [1] 310628 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Wesley Medical Research
Address
The Wesley Hospital. Auchenflower 4066
451 Coronation Drive
Brisbane QLD
Country
Australia
Secondary sponsor category [1] 311836 0
None
Name [1] 311836 0
Address [1] 311836 0
Country [1] 311836 0
Other collaborator category [1] 282143 0
University
Name [1] 282143 0
University of New England
Address [1] 282143 0
University of New England
Elm Avenue
Armidale, NSW 2351
Country [1] 282143 0
Australia
Other collaborator category [2] 282144 0
Other Collaborative groups
Name [2] 282144 0
Queensland Institute of Medical Research - Berghofer
Address [2] 282144 0
300 Herston Road, Herston QLD 4006
Country [2] 282144 0
Australia
Other collaborator category [3] 282218 0
Other
Name [3] 282218 0
Icon Cancer Centre
Address [3] 282218 0
1/40 Chasely St
Auchenflower 4066
Queensland
Country [3] 282218 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 310231 0
UnitingCare Health Human Research Ethics Committee
Ethics committee address [1] 310231 0
The Wesley Hospital
PO Box 499
Auchenflower
Queensland 4066
Ethics committee country [1] 310231 0
Australia
Date submitted for ethics approval [1] 310231 0
01/02/2022
Approval date [1] 310231 0
Ethics approval number [1] 310231 0

Summary
Brief summary
Recent studies on melanoma have shown that survival and response to treatment can related to gut microbiome diversity and richness. All bacteria produce molecules, known as metabolites, that can alter immune cell function. This study aims to assess whether people with melanoma who are being treated with a checkpoint inhibitor (immunotherapy) have any key differences in their bacterial metabolites (metabolome) that may determine whether they are likely to respond to their immunotherapy treatment.

Who is it for?
You may be eligible for this study if you are an adult aged 18 years or older, you have been diagnosed with resected and unresectable melanoma and you are undergoing checkpoint inhibitor therapy.

Study details
All participants who choose to enrol in this study will be asked to provide a blood sample and a faecal (stool) sample for testing. This will occur during a clinic appointment lasting no more than 20 minutes. Participants will be asked to provide these samples at the time of enrolment, at 6 weeks and then either (i) at the 6 month mark, or (ii) earlier if the immunotherapy treatment stops working.

It is hoped this research will determine if there are any key metabolite differences between melanoma patients who do respond to immune checkpoint inhibitor therapy, and those do not respond to this treatment. We hope to use our research findings to investigate more effective cancer treatments for patients in the future.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 116934 0
Dr Agnieszka Malczewski
Address 116934 0
Icon Cancer Centre
1/40 Chasely St,
Auchenflower 4066
Country 116934 0
Australia
Phone 116934 0
+61737374640
Fax 116934 0
Email 116934 0
[email protected]
Contact person for public queries
Name 116935 0
Dr Agnieszka Malczewski
Address 116935 0
Icon Cancer Centre
1/40 Chasely St,
Auchenflower 4066
Country 116935 0
Australia
Phone 116935 0
+61732327000
Fax 116935 0
Email 116935 0
[email protected]
Contact person for scientific queries
Name 116936 0
Dr Agnieszka Malczewski
Address 116936 0
Icon Cancer Centre
1/40 Chasely St,
Auchenflower 4066
Country 116936 0
Australia
Phone 116936 0
+61732327000
Fax 116936 0
Email 116936 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.