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BRIEF TITLE: Urinary Biomarkers in the Detection of Urothelial Carcinoma of the Bladder

Urinary Biomarkers in the Detection of Urothelial Carcinoma of the Bladder


  • Org Study ID: 151565
  • Secondary ID:
  • NCT ID: NCT02745301
  • NCT Alias:
  • Sponsor: Vanderbilt University - Other
  • Source: Vanderbilt University Medical Center

Brief Summary

To assess the persistence of bladder cancer-specific biomarkers in urine collected pre-operatively, in resected cancer tissue, and in urine collected post-operatively. A panel of sensitive and specific bladder cancer biomarkers will be used to establish a signature of disease in pre-operative patients with a positive diagnosis for bladder cancer by current standard of care (e.g., in-office cystoscopy, OR cystoscopy). The specificity of these markers will be assessed, as well as the degree of non-specific signal attributable to other sources of biomolecules, by analyzing resected tumor tissue for the same biomarkers. Finally, post-operative urine will be assessed for the presence of these markers. To the extent this biomarker panel can be determined to be specific and sensitive, it may serve as an indicator of the degree to which the surgical intervention successfully eradicated the underlying disease. The investigators also aim to assess the stability of a biomarker signature in urine but evaluating several patient specimens over various time points throughout the day.

Detailed Description


Current standard of care in non-muscle invasive bladder cancer (NMIBC) relies on pathologic
confirmation of negative margins as well as repeat transurethral resection. National
Comprehensive Cancer Network (NCCN) and American Urological Association (AUA) guidelines
specify a regular schedule of continued examination by cystoscopy and cytology to monitor the
patient for the recurrence of disease.

Physicians Choice Laboratory Services (PCLS) is validating a panel of biomarkers isolated
from voided urine for their combined ability to reliably detect the presence of transformed
cell populations. These markers include somatic mutations in a number of oncogenes that have
been well established as important etiologic factors in the development of bladder cancer in
the scientific and clinical literature. In addition, regional hypermethylation of the genome
is evaluated, as is the presence or absence of specific proteins involved in the disease
state. Through measurement of these biomarkers using next generation sequencing and
immunoassays, PCLS has been able to establish both the analytical and clinical validity of
these markers in diagnosing disease. The statistical correlation of these biomarkers with the
presence of transitional cell carcinoma has resulted in the ability to define a distinct
disease signature indicative of disease in preliminary studies. The current study aims to
expand upon these findings in an effort to offer physicians an additional tool with which to
manage bladder cancer.

Hypothesis: Bladder cancer biomarkers will be elevated in preoperative and intraoperative
urine specimens with direct correlation to the intact lesion(s), but will diminish
significantly or disappear in urine specimens post-operatively with as a function of
completion of resection. Further, the persistence of disease-specific biomarkers in urine
post-operatively may correlate with the risk of recurrence or progression.

Biomarker levels will be determined from pre-, intra- and post-operative urine specimens, as
well as from resected bladder tissue and will be statistically compared for changes that
correlate with presence or absence of visible disease. Biomarkers from tissue samples will be
quantified and compared with urine sample values.

The specific aims of the current proposal are to:

SA1): Assess the stability of a biomarker signature in urine. To date, efforts across the
biomarker field have relied on the detection of cancer in the context of a single patient
specimen collected at a single point in time. The consistency of the biomarker signature
across specimens provided by the same patient has not been fully described. The current study
will assess the consistency with which the biomarkers composing the panel can be detected
across urine specimens collected at multiple points in time in a subset of patients. This
data will inform the utility of single point-in-time collection with regard to accurately
defining the disease signature.

SA2): Assess the persistence of bladder cancer-specific biomarkers in urine collected
pre-operatively, in resected cancer tissue, and in urine collected post-operatively. A panel
of sensitive and specific bladder cancer biomarkers will be used to establish a signature of
disease in pre-operative patients with a positive diagnosis for bladder cancer by current
standard of care (e.g., in-office cystoscopy). The specificity of these markers will be
assessed, as well as the degree of non-specific signal attributable to other sources of
biomolecules, by analyzing resected tumor tissue for the same biomarkers. Finally,
post-operative urine will be assessed for the presence of these markers. To the extent this
biomarker panel can be determined to be specific and sensitive, it may serve as an indicator
of the degree to which the surgical intervention successfully eradicated the underlying
disease.

SA3): Determine whether persistence of biomarkers in patient urine post-operatively
correlates with recurrence or progression. The same panel of markers detected in the
pre-operative urine and tumor will be assayed in voided urine collected during routine
follow-up surveillance visits for a period of one year. Biomarkers will be monitored for
persistence and quantitative change in levels.

Overal Status Start Date Phase Study Type
Recruiting Start Date: April 2016 N/A Observational

Primary Outcomes:

Primary Outcome 1 - Measure: Change in urinary biomarker value from baseline following removal of bladder tumor

Primary Outcome 1 - Time Frame: An average of 1 month after surgery

Condition:

  • Bladder Cancer, Biomarkers

Eligibility

Criteria:
Inclusion Criteria:

- Suspected or confirmed urothelial type bladder cancer

- Scheduled for a transurethral resection of bladder tumor (TURBT) or cystectomy

Exclusion Criteria:

- Less than 18 years of age
<br/> - Known concurrent upper urinary tract disease

- History of bladder or prostate radiation

- Patients who are unwilling or unable to give consent
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: Accepts Healthy Volunteers

Official Information

Name: Kristen R Scarpato, MD

Role: Principal Investigator

Affiliation: Vanderbilt University

Overall Contact

Name: Pamela Steele, RN

Phone:

Email: pamela.steele@vanderbilt.edu

Location

Facility Status Contact
The Vanderbilt Clinic, VUMC
Nashville, Tennessee 37232
United States
Recruiting Pamela Steele, RN, BSN
615-343-2120
pamela.steele@vanderbilt.edu