Clinical Trial on Cancer, Urinary Bladder Cancer, Urothelial Cancer, Bladder Neoplasms - Clinical Trials Registry

Study Overview

Status

Recruiting

Conditions

Detailed Description

Bladder cancer is one of the most common malignancies worldwide. The rate of occurrence of these tumors is highest in the developed countries, ranking as the sixth most frequent neoplasm. Approximately 90% of malignant tumors arising in the bladder are of epithelial origin, the majority being transitional cell carcinomas. Early stage bladder tumors have been classified into two groups with distinct behaviors and different molecular profiles: Low-grade tumors (always papillary and usually superficial), and high-grade tumors (either papillary or non-papillary and often invasive). Clinically, superficial bladder tumors (stages Ta, Tis and T1) account for 75-80% of bladder neoplasms, while the remaining 15-20% are invasive (T2, T3, T4) or metastatic lesions at the time of presentation. Over 70% of patients affected with superficial tumors will have one or more recurrences after initial treatment, and about one-third of those patients will progress and eventually succumb to their disease.

Previous publications from this Urology Department have introduced the idea of a non-invasive, molecular-based assay for the detection and monitoring of bladder cancer (Levesque et al. 1993; Fitzgerald et al. 1995). At the time of publication there was limited knowledge of molecular changes underlying the different clinical pathways outlined above and our assay was based on one gene (c-H-ras-1). In the last few years, it has become clear that activation events associated with FGFR-3 can be found associated with 40%-60% of low-grade, low-stage bladder tumors whilst p53 mutations are linked to a more aggressive phenotype progressing via the CIS pathway. Mutations found in the c-H-ras-1 gene can straddle both of these groups. We propose to assess the use of a multiple mutation-based assay, using DNA from exfoliated cells in the urine of patients, to establish the sensitivity and specificity in tumor detection compared to cystoscopy and cytology. In addition, we propose to isolate free-DNA for use in molecular assays. The remaining urine will be stored to evaluate biomarkers for the detection of tumor presence or progression using protein-based analyses.

Cancer Patient Group:

All patients harboring tumors and scheduled to have a cystectomy, cystoscopy,or nephroureterectomy will be eligible for this study. This will include patients at first presentation and those who are in follow-up. Urine samples collected at the time of a procedure will be obtained from catheterized urine in the operating room. Urine obtained in the clinic setting will be obtained via voiding, as with standard urine sample collection. We propose to collect urine from study participants who have a cystoscopy on each occasion that they visit the Urology Department regarding the treatment and follow-up of their disease. The urine will be collected at intervals over a two-year period.

Control Patient Group:

The cancer assays to be tested use DNA analysis and antibodies to specific proteins as well as functional assays for proteins to attempt to identify bladder tumor presence. It is important to know whether other changes, including kidney stones, cystitis etc. cause the release of the same DNA or proteins into the urine as was found in cancer patients. The frequency of false positive results will determine the utility of the assay in the cancer detection arena. A patient group of age-matched controls will be recruited from the aforementioned patient populations requiring a single urine donation at the time of their scheduled clinic visit.

The primary objective of this study is to evaluate the utility of emerging technologies in the detection of bladder tumor cells using non-invasive approaches utilizing voided urine samples. This will include methodologies than can establish the sensitivity of detection of specific mutations associated with bladder cancer progression and the utility of this approach in complementing cystoscopy and cytology. The mutation status of amplified DNA fragments will be established using multiple molecular techniques. We will also isolate free-DNA from urine and perform extended-PCR to ascertain the proportional representation of large DNA fragments i.e. >1,500bp as an indicator of apoptotic activity and evaluate microRNA profiles from the urine samples.

Urine-borne exfoliated cells will be pelleted from urine collections using centrifugation and DNA/RNA will be extracted. The urine supernatant will be run over a DNA affinity column to capture free-DNA for analysis. Nucleic acids isolated from these procedures will be analyzed using PCR and various molecular technologies to establish the mutation status at different gene loci. The remaining urine will be frozen and used in protein detection assays using a panel of biomarkers with putative prognostic significance.

Detection of tumor presence will be compared in urine specimens undergoing mutational analysis and the current standard of treatment (cytology and cystoscopy together). As cytology is not performed on all patients, fewer urine specimens are expected in the cytology and cystoscopy group than in the mutational analysis group. Therefore a comparative analysis between these two groups will be performed using an analysis of variance (ANOVA) test where significance will be set at p<0.05.

Study Type

Observational

Enrollment (Estimated)

500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Kimberly Rieger-Christ, PhD
Phone Number: 781-744-2969
Email: Kimberly.R.Christ@lahey.org

Study Contact Backup

Name: Linda M. Topjian
Phone Number: 781-744-8711
Email: Linda.M.Topjian@Lahey.org

Study Locations

United States
- Massachusetts
  - Burlington, Massachusetts, United States, 01805
    - Recruiting
    - Lahey Clinic, Inc.
    - Sub-Investigator:
      
      Arthur Mourtzinos, M.D.
    - Sub-Investigator:
      
      Andrea Sorcini, M.D.
    - Sub-Investigator:
      
      Ali Moinzadeh, M.D.
    - Sub-Investigator:
      
      David Canes, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Lahey Clinic patients presenting to the Department of Urology and Primary Care Referrals

Description

Inclusion Criteria:

Patients scheduled to have a nephroureterectomy, cystectomy, cytoscopy (newly diagnosed bladder cancer and those with recurrent disease in follow up)
Control Group: No known evidence of bladder cancer-one urine sample
> than 18 years of age

Exclusion Criteria:

< than 18 years of age

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Observational Models: Case-Control
Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
1 Bladder Cancer Group: Patients scheduled to have a cystectomy or cystoscopy of their bladder with possible removal or biopsy of bladder tumor or tissue. Two urine samples collected at the time of the scheduled procedure: One sample collected through voiding. The other sample collected from atheterized urine in the operating room. Additional urine samples may be collected at each follow up visit over two years. These samples will be obtained via voiding, standard urine sample collection.
2 Control Group: Patients with no known evidence of bladder cancer. One urine sample will be collected through voiding, as with standard urine sample collection at the time of clinic visit.

Group / Cohort

1

Bladder Cancer Group:

Patients scheduled to have a cystectomy or cystoscopy of their bladder with possible removal or biopsy of bladder tumor or tissue.

Two urine samples collected at the time of the scheduled procedure:

One sample collected through voiding. The other sample collected from atheterized urine in the operating room. Additional urine samples may be collected at each follow up visit over two years. These samples will be obtained via voiding, standard urine sample collection.

2

Control Group: Patients with no known evidence of bladder cancer. One urine sample will be collected through voiding, as with standard urine sample collection at the time of clinic visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the utility of emerging technologies in the detection of bladder tumor cells using non-invasive approaches utilizing voided urine samples. Time Frame: Ongoing Lab analysis for study duration: final data completion date	Ongoing Lab analysis for study duration: final data completion date

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lahey Clinic

Investigators

Principal Investigator: Kimberly Rieger-Christ, PhD, Lahey Clinic, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2002

Primary Completion (Estimated)

October 1, 2028

Study Completion (Estimated)

November 1, 2028

Study Registration Dates

First Submitted

March 27, 2009

First Submitted That Met QC Criteria