Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04100811 |
| Other study ID # |
MIR-P001 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
December 1, 2019 |
| 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
In this non-interventional study, men being seen by urologists in the course of their normal
practice that present with clinical suspicion of prostate cancer (based on DRE, elevated
Prostate Specific Antigen (PSA), and/or family medical history of prostate cancer, among
other reasons) and who meet the inclusion/exclusion criteria will be asked to consent to the
clinical study and provide a 40-60 mL urine sample, without prior DRE, along with relevant
de-identified clinical data, at the time of the initial consultation, prior to core-needle
biopsy.
The miR Scientific Sentinel® Prostate Cancer Classifier Platform (Sentinel® PCC4 Test) is a
new molecular test that interrogates 442 small non-coding RNAs (sncRNA) extracted from
urinary exosomes. Using the expression levels of 442 sncRNAs isolated from urine exosomes,
the Sentinel® PCC4 Test provides an initial classification of disease status as either no
molecular evidence of prostate cancer (NMEPC), or molecular evidence (MEPC) of low-,
intermediate- or high-risk of aggressive prostate cancer. This study is designed to validate
the classification algorithm and finalize the performance characteristics of the Test using
risk-group labeling based on pathological grading from core-needle biopsy data.
Description:
The miR Scientific Sentinel® Prostate Cancer Classifier Platform (Sentinel® PCC4 Test) is a
new molecular test that interrogates 442 small non-coding RNAs extracted from urinary
exosomes. The Sentinel® PCC4 Test provides urologists with an early, non-invasive and precise
indication of disease status in men presenting with clinical suspicion of prostate cancer.
The test provides an initial classification of disease status as either no molecular evidence
of prostate cancer (NMEPC), or molecular evidence (MEPC) of low-, intermediate- or high-risk
of aggressive prostate cancer. The current standard of care (SOC) assesses the risk of
prostate cancer based on information that includes a suspicious DRE, and "elevated" serum PSA
(commonly greater than 3ng/mL based on the current NCCN guidelines, but in clinical practice
can frequently be less than or greater than 3ng/mL, depending on the practice). The estimated
sensitivity (44%) and specificity (68%) of the current SOC means that a significant portion
of prostate cancer cases are not identified, and many biopsies with resulting co-morbidities
are unnecessary.
Patients who enroll in this study will receive the current SOC and have a TRUS- or MRI-guided
fusion core needle biopsy. Biopsies will be read by pathologists associated with each
participating clinical institution at which the biopsy was performed. The Gleason score,
tumor staging, and anatomic location for each positive core will be collected at each site,
and barcoded urine samples will be couriered overnight to the miR Scientific laboratories for
Sentinel® PCC4 Test analysis. To minimize the potential for inter-observer variability, the
pathology of the core needle biopsies for each patient will also be reviewed by an
independent central pathologist, not associated with miR Scientific.
After assessing the pathology, anatomic contribution and additional clinical data
(particularly DRE and serum PSA levels) that inform Grade Group assessment and the NCCN risk
assessment, the final risk group assessment for both Primary Study Objective #1 and Primary
Study Objective #2 will be determined by the pathologist. The final risk group determination
for each patient will be used individually to represent the risk status provided by the
current SOC for comparison to the molecular classifications provided by the Sentinel® PCC4
Test.
The performance of the Sentinel® PCC4 Test to classify the disease status of a future patient
(with unknown true disease status) as either no molecular evidence of prostate cancer or, for
patients with molecular evidence of prostate cancer, as having low-risk, intermediate-risk or
high-risk of aggressive prostate cancer will be established for both Primary Study
Objectives.
Primary Study Objective #1: To establish the performance characteristics of the Sentinel®
Prostate Cancer Classifier Platform (Sentinel® PCC4 Test) using pathological grading (Grade
Grouping based on Gleason score as proposed by Epstein and colleagues in 2013) as the
comparative basis for assessing the prostate health of men aged 45-75 years presenting with
suspicion of prostate cancer.
The performance characteristics of the Sentinel® PCC4 Test as described via the Primary Study
Objectives will be assessed in comparison to core needle biopsy report using pathology
Gleason score grading (Grade Group) risk classifiers where GG1 is indicative or low-risk, GG2
as intermediate risk and GG3-5 as high-risk of aggressive prostate cancer. The sensitivity,
specificity, positive and negative predictive values of the Sentinel® PCC4 Test for
risk-classification in concordance with the GG-risk assessment will be established.
Primary Study Objective #2: To establish the performance characteristics of the Sentinel®
PCC4 Test when using the modified risk assessment criteria recently recommended by the
National Comprehensive Cancer Network (NCCN) as the basis for assessing the prostate health
of men aged 45-75 years presenting with suspicion of prostate cancer.
In addition to the pathological grade of the tumor, the NCCN risk assessment incorporates
additional clinical measures associated with tumor progression, including number of positive
cores, percent tumor involvement per core, tumor stage (anatomical location of positive
cores), serum PSA and PSA density. The same molecular expression data from the Sentine® PCC4
Test will be used to evaluate both Primary Objectives for each patient.
Statistical Methodology: This study will enroll patients visiting urology clinics for initial
clinical workup based on any clinical suspicion of prostate cancer. The study will evaluate
the properties of the Sentinel® PCC4 Test that is based on use of a proprietary
classification system to identify patients with no molecular evidence of prostate cancer and
to initially classify the risk of prostate cancer patients.
For a given two-group comparison, the proprietary Classification Algorithm controls
sensitivity for a patient with unknown true disease status at or above a pre-specified level,
denoted 1-α; for example, the value that has been assumed in this design is α=0.05. Note that
the value of α represents the false-negative rate of the test for the given two-group
comparison.
The initial nominal labeling of clinical groups will be done separately when using the
Gleason Grade group (Primary Study Objective #1) and recent NCCN definitions (Primary Study
Objective #2) as described in detail above. Cross-validation will be used in the training
dataset to determine the classification cut-offs for a given two-group comparison in the
Sentinel® PCC4 Test. A general description of this procedure is as follows. For each
participant in the training dataset (current participant), a two-group classification for
this current participant will be determined based on the remaining members of the training
dataset using only the current participant's sncRNA sequence; the accuracy of this
determination will be assessed by comparison of the group classification determined to the
actual label given to the current participant (either Grade Group or NCCN group). That is,
the disease status label of the current participant in the training dataset will be blinded,
thereby mimicking the setting for classification of a future patient. This procedure is then
repeated separately for each subject in the training dataset. The tuning parameters and
cutoff boundary used for each of the two-group classifications comprising the Sentinel® PCC4
Test are then calculated so that the empirical sensitivity over participants in the training
dataset is at least 1-α.
With these cut-offs and classification rules determined using the training dataset for the
Sentinel® PCC4 Test, the Sentinel® PCC4 classifications for each member of the validation
dataset will be determined using only information generated from their expression levels of
the sncRNA sequences; the corresponding results will be stored in a date-stamped, locked file
as described above. The clinical risk group for each member of the validation dataset as
determined by the central pathologist will also be stored in a locked and date-stamped file.
When both files are completed, they will be released to the miR Scientific team and the
performance characteristics of the Sentinel® PCC4 Test established in the validation dataset;
note that these error rates refer to the classification of a future patient with unknown
disease status.
