Assessement of the Concordance of Genomic Alterations Between Urine and Tissue in High-Risk NMIBC Patients

NCT04412070 | Terminated

• 1 other identifier: 2018_0087
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The analysis of cell-free tumor DNA (cfDNA) in plasma has emerged as a clinically relevant predictive and prognostic biomarker in several metastatic solid malignancies, and even now represents standard-of-care for prescription of some targeted therapies in non-small cell lung cancer (blood-based T790M companion diagnostic test). cfDNA can be detected not only in plasma but also in urine, even in patients with non-invasive disease. Recent studies found that the detection of genomic alterations in plasma of urothelial bladder carcinoma patients was relatively uninformative in the localized setting. However, urine cfDNA has been shown to provide a promising resource for robust whole-genome tumor profiling in clinically localized Muscle invasive Bladder cancer (MIBC) and Non-Muscle Invasive Bladder Cancer (NMIBC). Genomic alterations using a targeted next-generation sequencing (NGS) panel have been recently documented in a series of treatment-naïve high-risk NMIBC. The investigator's aim is to determine whether liquid biopsies can be used as a new diagnostic assay to guide immunotherapeutic approaches in patients with high-risk NMIBC. The ultimate goal is to develop a "testing decision tree" to segment patients for informing on therapeutic decision and customizing treatment.

Conditions

Bladder Cancer

Keywords

Muscle Invasive Bladder Cancer; Non-Muscle Invasive Bladder Cancer; cfDNA

Outcome Measures

Primary Outcomes (1)

• Agreement rate between urine cell-free DNA and tumor tissue mutation profile

  concordance rate between mutations identified in the tumor

  Day 0

Secondary Outcomes (1)

• Prognostic value of Tumor Mutation Burden (TMB)

  Day 0

Study Arms (2)

Patient with Non-Muscle invasive Bladder Cancer

Patients in this group will be enrolled before the start of their treatment with BCG. This will start within 4 weeks after the transurethral bladder resection, in accordance with the guidelines

Patient with Muscle Invasive Bladder Cancer

Patients in this group will be enrolled in the study before surgical treatment by radical cystectomy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population concerns : * Group 1 : patients with high-risk NMIBC treated by BCG therapy * Group 2 : patients with MIBC treated by radical cystectomy. This group will be considered as a positive control. During their conventional follow-up, a urine collection will be performed to each patient for testing of cell-free DNA. Genomic analysis of the primary tumor will be carried out on the tumor samples resetced during the initial diagnosis.

You may qualify if:

• Age ≥18 years at the time of screening.
• Capable of giving signed informed consent
• BCG-naïve (patients who have not received prior intravesical BCG or who previously received but stopped BCG more than 3 years before study entry are eligible).
• No prior radiotherapy to the bladder.
• ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1.
• At screening, tumor tissue provision from the initial surgery, formalin-fixed and paraffin-embedded (FFPE) is mandatory for DNA extraction and next-generation sequencing.
• Absence of metastasis, as confirmed by a negative CT or MRI scan of the pelvis, abdomen and chest, no more than 4 weeks prior to the enrolment.
• Life expectancy of at least 12 weeks.
• Must be a candidate for BCG treatment.
• Adequate organ and marrow function as defined below:
• Hemoglobin ≥9.0 g/dL Absolute neutrophil count ≥1.0 × 109/L Platelet count ≥75 × 109/L Serum bilirubin ≤1.5 × the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome, who will be allowed in consultation with their physician.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN Measured creatinine clearance (CL) \>40 mL/min or calculated creatinine CL \>40 mL/min as determined by Cockcroft-Gault (using actual body weight) Males Creatinine CL = (Weight (kg) × (140 - Age))/(72 × serum creatinine (mg/dL)) (mL/min)
• Females Creatinine CL = (Weight (kg) × (140 - Age) )/(72 × serum creatinine (mg/dL)) × 0.85 (mL/min) - Being covered by a national health insurance
• Local histological confirmation (based on pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa (predominantly urothelial even though mixed histology are allowed). A high-risk tumor is defined as one of the following:
• T1 tumor

Sponsors & Collaborators

• Hopital Foch: lead
• AstraZeneca: collaborator

Study Sites (1)

Foch hospital

Suresnes, 92151, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

* One urine sample previously collected during patient's initial treatment and stored at the Biological Resources Center of Foch Hospital * Urine samples collected before each BCG (bacille Calmette Guerin) instillation * One blood sample collected before treatment with BCG during inclusion visit * One tumor sample previously collected during patient's initial treatment and stored in paraffin at the pathology department of Foch Hospital * One tumor sample collected in case of relapse during the 24 months follow-up

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Yanish Soorojebally, MD

  Hopital Foch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 2, 2020
• Study Start: July 30, 2021
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)