A Pilot Study to Assess the Concordance of Genomic Alterations Between Urine and Tissue to Develop Precision Medicine-Based Immunotherapy Approaches in High-Risk NMIBC Patients
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Bladder Cancer
- Sponsor
- Hopital Foch
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Agreement rate between urine cell-free DNA and tumor tissue mutation profile
- Status
- Terminated
- Last Updated
- 5 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Common Inclusion Criteria
- •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
- •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.
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Agreement rate between urine cell-free DNA and tumor tissue mutation profile
Time Frame: Day 0
concordance rate between mutations identified in the tumor
Secondary Outcomes
- Prognostic value of Tumor Mutation Burden (TMB)(Day 0)