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Trial registered on ANZCTR


Registration number
ACTRN12608000048381
Ethics application status
Approved
Date submitted
23/01/2008
Date registered
29/01/2008
Date last updated
14/12/2009
Type of registration
Prospectively registered

Titles & IDs
Public title
The uRNA study for the detection of bladder cancer
Scientific title
A prospective study of a novel urine diagnostic test for the detection of urinary tract transitional cell carcinoma
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bladder cancer 2738 0
hematuria 2739 0
Condition category
Condition code
Cancer 2864 2864 0 0
Bladder

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
A diagnostic test (uRNA) that quantitates four messenger ribonucleic acid (mRNA) molecules in unfractionated urine. Patients provide a single urine sample prior to cystoscopy. The sample is put into a buffering solution, then the levels of mRNAs in the sample determined.
Intervention code [1] 2479 0
Early detection / Screening
Comparator / control treatment
The test will be applied to a prospective series of patients presenting with macroscopic hematuria. The same urine samples will be tested with the FDA-approved urine tests NMP22 ELISA and NMP22 BladderChek. The uRNA and NMP22 tests will be compared with the standard of care which is cystoscopy combined with urine cytology.
Control group
Active

Outcomes
Primary outcome [1] 3748 0
To determine the characteristics (sensitivity, specificity, area under the ROC curve, positive and negative predictive values) of the uRNA-D test for the detection of TCC in patients with a recent history of gross haematuria. Timeline: disease diagnosis will be determined by the standard of care (urine cytology, cystoscopy) within 3 months of the patient being recruited. Sensitivity and specificity will be measured by comparison to standard clinical practice (cystoscopy combined with cytology).
Timepoint [1] 3748 0
Patients will provide a urine sample at the time of recruitment. No other samples will be taken.
Secondary outcome [1] 6330 0
1. To compare the characteristics (sensitivity, specificity, positive and negative predictive values) of the uRNA-D test to those of the NMP22 ?BladderChek Test?.
Timepoint [1] 6330 0
Patients will provide a urine sample at the time of recruitment. No other samples will be taken.
Secondary outcome [2] 6331 0
2. To compare the characteristics (sensitivity, specificity, positive and negative predictive values) of the uRNA-D test to those of the NMP22 ELISA test kit.
Timepoint [2] 6331 0
Patients will provide a urine sample at the time of recruitment. No other samples will be taken.
Secondary outcome [3] 6332 0
3. To compare the results of the uRNA-D test and those of the NMP22 ELISA test kit and the NMP22 ?BladderChek Test? to those of urine cytology according to presence or absence of TCC, where diagnosis was based on biopsies of lesions identified as suspicious at cystoscopy, without consideration of cytology results.
Timepoint [3] 6332 0
Patients will provide a urine sample at the time of recruitment. No other samples will be taken.
Secondary outcome [4] 6333 0
4. To compare the sensitivity and specificity of the uRNA-D test by stage (Ta vs Tis, T1-T3) and grade (3 vs 1 and 2) with that of the NMP22 ELISA test, the NMP22 ?BladderChek Test? and urine cytology.
Timepoint [4] 6333 0
Patients will provide a urine sample at the time of recruitment. No other samples will be taken.
Secondary outcome [5] 6334 0
5. To estimate the sensitivity, specificity and positive and negative predictive values of the combination of uRNA-D and uRNA-S in diagnosing
a. T1-T3 TCC
b. grade 3 TCC
c. stage T1-T3 or grade 3 TCC.
Timepoint [5] 6334 0
Patients will provide a urine sample at the time of recruitment. No other samples will be taken.
Secondary outcome [6] 7089 0
6. To compare the sensitivity and specificity of the uRNA-D test and the NMP22 tests in test samples which contain detectable levels of blood.
Timepoint [6] 7089 0
7. To collect urine samples from patients with a history of gross haematuria, for the further refinement and development of urine tests for the diagnosis and management of bladder cancer.

Eligibility
Key inclusion criteria
1.Patients presenting with a recent history of primary gross haematuria and who require further investigation for possible urological cancer
2. No previous investigations for urinary tract cancer or TCC (with the exception of radiological imaging eg CT scan / ultrasound, or bloods)
3. Able to provide a voided urine sample
4. Able to give written informed consent
5. Able and willing to comply with study requirements
6. > 18 years
Minimum age
45 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will not have any of the following: 1. Prior history of bladder malignancy, prostate or renal cell carcinoma 2. Ongoing gross haematuria less than 24 hrs prior to investigation 3. Prior genitourinary manipulation in the 14 days before urine collection 4. Current urinary tract infection 5. Current or known history of urinary tract inflammatory disorder 6. Active renal disorders which may cause haematuria eg pyelonephritis, glomerulonephritis, nephrosis, or other renal inflammatory disorders 7. Current or intermittent catheterisation within 5 days of urine sample collection 8. Recent history of pyelonephritis 9. Previous alkylating based chemotherapy 10. History of renal or pelvic trauma within last 3 months 11. Previous cystoscopy for the investigation of haematuria in the 12 months before enrolment.
12. Cystoscopy for any reason in the 6 months before enrolment.

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Case control
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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)
Recruitment postcode(s) [1] 1385 0
3050
Recruitment postcode(s) [2] 1386 0
3165
Recruitment outside Australia
Country [1] 741 0
New Zealand
State/province [1] 741 0
Waikato
Country [2] 742 0
New Zealand
State/province [2] 742 0
Southland
Country [3] 743 0
New Zealand
State/province [3] 743 0
Northland
Country [4] 744 0
New Zealand
State/province [4] 744 0
Nelson
Country [5] 745 0
New Zealand
State/province [5] 745 0
Bay of Plenty
Country [6] 746 0
New Zealand
State/province [6] 746 0
Auckland
Country [7] 747 0
New Zealand
State/province [7] 747 0
Counties/Manakau
Country [8] 748 0
New Zealand
State/province [8] 748 0
Canterbury
Country [9] 749 0
New Zealand
State/province [9] 749 0
Wellington

Funding & Sponsors
Funding source category [1] 3005 0
Commercial sector/Industry
Name [1] 3005 0
Pacific Edge Biotechnology Ltd
Address [1] 3005 0
Centre for Innovation
87 St David St
Dunedin
Country [1] 3005 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Pacific Edge Biotechnology Ltd
Address
Centre for Innovation
87 St David St
Dunedin
Country
New Zealand
Secondary sponsor category [1] 2709 0
None
Name [1] 2709 0
n/a
Address [1] 2709 0
n/a
Country [1] 2709 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4963 0
New Zealand Multi-region ethics committee
Ethics committee address [1] 4963 0
P.O. Box 5013
Wellington
Ethics committee country [1] 4963 0
New Zealand
Date submitted for ethics approval [1] 4963 0
24/11/2006
Approval date [1] 4963 0
23/03/2007
Ethics approval number [1] 4963 0
MEC/06/12/176

Summary
Brief summary
Prior case-control studies on selected samples showed highly promising levels of sensitivity and specificity for uRNA.
The next phase in the evaluation of the uRNA tests is to carry out a nested case-control study in a clinical population in which uRNA could potentially be useful. This would enable more accurate estimations of sensitivity and specificity as well as estimations of positive and negative predictive values for this population. This study would also enable a formal comparison of sensitivity and specificity for uRNA and each of the FDA-approved NMP22 tests.
The clinical population chosen for this phase is patients with no history of TCC who present with a history of gross haematuria. This is the most common presentation for TCC and forms a relatively well defined population. In this study’s patient population, the potential use of uRNA is in conjunction with cystoscopy, where it would aim to identify TCCs which were missed during initial cystoscopy. Currently cytology is routinely used for this purpose and an alternative non-invasive assay NMP22 (Matritech) is also FDA approved for use, although it is not in routine use.
The nested case control study described here will explore the value of uRNA as an adjunct to cystoscopy and in particular compare the performance of uRNA to that of cytology and the NMP22 tests for the detection of primary TCC in patients with a history of gross haematuria. Of particular interest are the relative sensitivity, specificity, positive and negative predictive values, the variation in sensitivity and specificity by grade and stage of disease, and the ability of the tests to identify invasive TCC.
Trial website
n/a
Trial related presentations / publications
Development of a Multiplex RNAUrine Test for the Detection and Stratification ofTransitional Cell Carcinoma of the Bladder.
Andrew Holyoake, Paul O’Sullivan, Rob Pollock, Terry Best, Jun Watanabe, Yoichiro Kajita, YoshiyukiMatsui, Masaaki Ito, Hiroyuki Nishiyama, Natalie Kerr, Fernanda da Silva Tatley, Lisa Cambridge, Tumi Toro, Osamu Ogawa and Parry Guilford. Clinical Cancer Research, in press.
Public notes

Contacts
Principal investigator
Name 28314 0
Address 28314 0
Country 28314 0
Phone 28314 0
Fax 28314 0
Email 28314 0
Contact person for public queries
Name 11471 0
Parry Guilford
Address 11471 0
c/o Pacific Edge Biotechnology Ltd
Centre for Innovation
87 St David St
Dunedin
Country 11471 0
New Zealand
Phone 11471 0
64 3 4795803
Fax 11471 0
64 3 4795801
Email 11471 0
parry.guilford@peblnz.com
Contact person for scientific queries
Name 2399 0
Parry Guilford
Address 2399 0
c/o Pacific Edge Biotechnology Ltd
Centre for Innovation
87 St David St
Dunedin
Country 2399 0
New Zealand
Phone 2399 0
64 3 4795803
Fax 2399 0
64 3 4795801
Email 2399 0
parry.guilford@peblnz.com

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