Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000864628
Ethics application status
Not yet submitted
Date submitted
21/07/2014
Date registered
12/08/2014
Date last updated
12/08/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Immunosuppression dose reduction to prevent development of aggressive skin cancer after kidney transplantation
Scientific title
Prospective Randomized Controlled Trial of Monitored Immunosuppression Dose Reduction for Secondary Prevention of Squamous Cell Carcinoma of the Skin in Kidney Transplant Recipients
Secondary ID [1] 285030 0
NIL
Universal Trial Number (UTN)
U1111-1159-4876
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
skin cancer 292539 0
kidney transplantation 292540 0
Condition category
Condition code
Cancer 292846 292846 0 0
Non melanoma skin cancer
Renal and Urogenital 292847 292847 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Reduction in immunosuppression: Tacrolimus, Cyclosporin and Mycophenolate will be reduced on average by 25% based on drug exposure profiles. All these medications are dosed twice a day. The dose reduction will occur at a single time point and the drug exposure profile measured 2 weeks later to determine whether subsequent reduction is required. If required again drug exposure will be checked two weeks later.
Intervention code [1] 289859 0
Prevention
Intervention code [2] 289959 0
Treatment: Drugs
Comparator / control treatment
Continued regimen of immunosuppression: In most cases a drug regimen will contain a calcineurin inhibitor (tacrolimus or cyclosporin) and an anti-proliferative agent (mycophenolate or azathiorprine). These medications are taken mostly twice a day and azathioprine is taken daily. Prednisolone is also take daily at doses between 5 and 10mg. All medications are taken orally and for as long as the renal transplant is functioning
Control group
Dose comparison

Outcomes
Primary outcome [1] 292712 0
Time to the development of first new squamous cell carcinoma of the skin after randomisation
Timepoint [1] 292712 0
New cancer development within 12 months
Secondary outcome [1] 309537 0
Proportion of new squamous cell carcinomas that develop with high risk features: poorly differentiated; >3mm thick;>6 mm thick;peri neural invasion
Timepoint [1] 309537 0
12 months
Secondary outcome [2] 309538 0
Acute rejection or chronic rejection after randomisation- according to standard histological grading systems of rejection that is Banff 2014 criteria
Timepoint [2] 309538 0
5 years post randomisation
Secondary outcome [3] 309539 0
worsening of renal function >20% in serum assay of creatinine
Timepoint [3] 309539 0
upto 5 years post randomization
Secondary outcome [4] 309774 0
Development of proteinuria >500 mg/l in those with pre- existing proteinuria >100mg/l. Development of >100mg proteinuria in those with undetectable proteinuria. All of these measurements are via standard laboratory assay of urinary protein and via spot urine specimens not timed 24 hour samples
Timepoint [4] 309774 0
upto 5 years post randomisation
Secondary outcome [5] 309776 0
development of donor specific antibodies as measured in sera by solid phase assay ie Luminex platform.
Timepoint [5] 309776 0
within 1 year of randomisation

Eligibility
Key inclusion criteria
Kidney transplant recipients with a previous squamous cell carcinoma of the skin
High levels of Regulatory T cells in peripheral blood
Low levels of allo reactive T cells measured by ELISPOT
Absence of donor specific allo antibodies
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Presence of a donor specific antibody
High levels of allo reactive T cells in peripheral circulation
Low levels of Regulatory T cells in blood

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)
Patients will be randomised to monitored dose reduction in immunosuppression or to remain on current drug regimen. Allocation will be concealed by sequentially randomising subjects via sequential opening of sealed opaque envelopes held in central administration site
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Transplant patients with previous skin cancer could tolerate a 25% reduction in immunousppression and this should equate to a 30% reduction in time to next skin cancer. Subjects with >19 Treg cells/ul blood have median time to next skin cancer 100 days and 86% chance that such skin cancer is aggressive histologically. With a power of 80%, 90 day lead in time, follow-up 365 days, significance of 0.05, 40 subjects are needed in each group. With a 5% drop in and 5% drop out; 98 subjects will need to be recruited. The study is concomitantly powered to detect reduction in the proportion of aggressive SCC that develop from 86% to 58%

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2014
Actual
Date of last participant enrolment
Anticipated
1/09/2016
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
98
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 2757 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 2758 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [3] 2759 0
Princess Alexandra Hospital - Woolloongabba

Funding & Sponsors
Funding source category [1] 289637 0
Charities/Societies/Foundations
Name [1] 289637 0
Australian and New Zealand Society of Nephrology
Country [1] 289637 0
Australia
Primary sponsor type
Individual
Name
Robert Peter Carroll
Address
Royal Adelaide Hospital
North Terrace
SA 5000
Country
Australia
Secondary sponsor category [1] 288326 0
Hospital
Name [1] 288326 0
Royal Adelaide Hospital
Address [1] 288326 0
North Terrace
Adelaide
SA5000
Country [1] 288326 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 291378 0
Royal Adelaide Hospital
Ethics committee address [1] 291378 0
Royal Adelaide Hospital
North Terrace
SA5000
Ethics committee country [1] 291378 0
Australia
Date submitted for ethics approval [1] 291378 0
04/08/2014
Approval date [1] 291378 0
Ethics approval number [1] 291378 0

Summary
Brief summary
This study will determine whether reducing the doses of anti-rejection drugs is effective in preventing squamous cell carcinoma of the skin in kidney transplant recipients. Who is it for? You may be eligible to join this study if you aged 18 years or above, are a kidney transplant recipient with a previous squamous cell carcinoma of the skin. Study details Participants in this study are randomly allocated (by chance) to one of two groups. Participants in one group will have monitored dose reduction in immunosuppression, whilst participants in the other group will remain on their current drug regimen. Participants will be follow-up for 60 months, in order to determine how many new squamous cell carcinomas develop and whether they are aggressive. There are several test of the immune system to make sure the risk of acute or chronic rejection is very low but your kidney function will be followed for up to 60 months to make sure the dose reduction is safe over the long term.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 50110 0
Dr Robert Peter Carroll
Address 50110 0
Central Northern Adelaide Renal and Transplant Service
Royal Adelaide Hospital
North Terrace
SA5000
Country 50110 0
Australia
Phone 50110 0
+61 8 82220900
Fax 50110 0
+61 8 82220970
Email 50110 0
robert.carroll@health.sa.gov.au
Contact person for public queries
Name 50111 0
Dr Robert Peter Carroll
Address 50111 0
Central Northern Adelaide Renal and Transplant Service
Royal Adelaide Hospital
North Terrace
SA5000
Country 50111 0
Australia
Phone 50111 0
+61 8 82220900
Fax 50111 0
+61 8 82220970
Email 50111 0
robert.carroll@health.sa.gov.au
Contact person for scientific queries
Name 50112 0
Dr Robert Peter Carroll
Address 50112 0
Central Northern Adelaide Renal and Transplant Service
Royal Adelaide Hospital
North Terrace
SA5000
Country 50112 0
Australia
Phone 50112 0
+61 8 82220900
Fax 50112 0
+61 8 82220970
Email 50112 0
robert.carroll@health.sa.gov.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
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Documents added automatically
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