Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04155359 |
| Other study ID # |
MIR-B001 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 13, 2020 |
| Est. completion date |
December 31, 2024 |
Study information
| Verified date |
October 2023 |
| Source |
miR Scientific LLC |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The purpose of the study is to establish the clinical performance and utility of the miR
Sentinel™ BCa Test, a urine exosome-based diagnostic test, as an aid in diagnosing bladder
cancer. Male and female participants presenting with micro- or macro-hematuria who are
undergoing cystoscopy for diagnosis of bladder cancer will be eligible for the study. Urine
samples will be collected at the time of the first presentation, and the miR Sentinel™ BCa
Score determined and compared to the results of cystoscopy. Participants with no evidence of
cancer following cystoscopy will be designated cancer-free, while those participants with a
positive cystoscopy and histopathological evidence of cancer will be designated as having
bladder cancer. Participants with a positive cystoscopy who subsequently undergo TURBT will
be eligible to continue in the study. Urine samples will be collected at each follow up visit
for up to three years, and the miR Sentinal™ BCR Score will be determined and compared to the
results of surveillance cystoscopy.
Description:
Primary Objective(s):
Establish the performance characteristics of the miR Sentinel™ BCa Test as an aid in
diagnosing bladder cancer in men and women presenting with hematuria.
Secondary Objective(s) Establish the performance characteristics of the miR Sentinel™ BCR
Test in identifying bladder cancer patients with recurrent disease.
Study Design:
Participants who present with evidence of hematuria (micro- or macro-hematuria) and are
scheduled to have cystoscopy will be enrolled. All participants will provide a urine sample
for the miR Sentinel™ BCa Test prior to cystoscopy for bladder cancer. The presence or
absence of cancer will be determined by cystoscopy. Diagnosis of bladder cancer will be
confirmed by histopathology. The performance of the miR Sentinel™ BCa Test for classifying
future patients as either bladder cancer or no bladder cancer will be established. The
sensitivity, specificity, positive and negative predictive value determined for the miR
Sentinel™ BCa Test and will be compared to cystoscopy.
Statistical Analysis:
Definitions. The general notation P(A | B) means the probability (prevalence) of the event A
among the subgroup of patients in a population all of whom have the event B.
1. Sensitivity = P(screening test + | disease).
2. Specificity = P(screening test - | no disease).
3. PPV = P(disease | screening test + ).
4. NPV = P(no disease | screening test -).
Estimate of Sample Size. This study is targeted to enroll 3000 participants, 1500 males and
1500 females, who present with hematuria. Approximately 15% of participants with hematuria
have bladder cancer; men have a higher incidence of bladder cancer than women. Therefore, the
investigators anticipate that 225 males (15% of all males enrolled) and 175 females
(approximately 12% of all women enrolled) will have bladder cancer confirmed by
histopathology.
Overview. As outlined below, this clinical study will enroll male and female participants
that have been identified as having (micro- or macro-) hematuria and are therefore at risk
for bladder cancer and meet clear eligibility criteria. The study will evaluate the miR
Sentinel™ BCa Test for classification of participants as cancer or no cancer, to be used as
an aid in diagnosing bladder cancer. For participants diagnosed with bladder cancer who
undergo TURBT will be eligible to continue in the study of miR Sentinel™ BCR Test to monitor
for recurrent disease in conjunction with the cystoscopy associated with the standard of care
recommended by the AUA.
The miR Sentinel™ BCa Test functions by controlling sensitivity at or above a pre-specified
level, denoted 1-α; where α is the false-negative rate of the test (a patient who truly has
bladder cancer has a negative test result), For example, the value that has been assumed in
this design is α≤0.05 so that sensitivity is at least 95%. To describe how the cutoff for the
miR Sentinel™ BCa Test is calculated to control sensitivity, for each participant determined
to have bladder cancer by histopathology, the miR Sentinel™ BCa Score will be calculated
using an approach that blinds each participant's true cancer status, mimicking the setting
for classification of a future patient. The cutoff value for the Sentinel™ Score is then
chosen so that the empirical sensitivity, calculated over all patients in the training
dataset, yields a 95% upper confidence interval with lower limit 1-α.
To provide some detail on the calculation of the error rates of the test, the method to be
used for estimation is cross-validation. Cross-validation produces unbiased estimators of
error rates for classification of a future patient, with unknown true disease status, as the
number of patients in the training dataset grows large. If there are 3000 participants with
hematuria divided equally from male and female population in the study and 225 males and 175
females with bladder cancer, then, for males, the upper 95% confidence interval based on an
observed empirical sensitivity of 97% (218/225) will have a lower bound of 0.95, and for
females, the upper 95% confidence interval based on an observed empirical sensitivity of 98%
(171/175) will have a lower bound of 0.95.
Validation of the miR Sentinel™ BCR for identifying patients with recurrent disease uses
essentially the same statistical methodology. However, the classification is based on the
comparison of the miR Sentinel™ BCR signature for patients with stable (non-recurrent
disease) and patients with evidence of progressive (recurrent) disease. The longitudinal
monitoring of participants diagnosed with bladder cancer by cystoscopy may provide additional
information related to anticipatory changes in the Sentinel™ signature indicative of
recurrence.
