A Study to Compare the Results of FGFR Testing by Either ctDNA Blood Testing or Standard Tumor Tissue Testing

Study Overview
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Brief Summary
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A new drug, erdafitinib, became available for some patients with bladder cancer that has spread to other organs. To qualify, patients must have specific genetic changes in their tumors. Currently, doctors use tumor tissue samples to check for these genetic changes, but these samples might not accurately reflect the current state of the patient's cancer. In this study, Investigators will test the patient's blood for these genetic changes in addition to the tumor tissue samples. It is thought that the blood test will give a more accurate result. Investigators hope this study will help to find out if more patients can benefit from erdafitinib than the ones identified by tissue testing only.

Detailed Description
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Recently, the first targeted therapy for patients with metastatic urothelial cancer (mUC) received approval, i.e. erdafitinib. Erdafitinib is a pan-FGFR small molecule inhibitor. Approximately twenty percent of mUC patients' tumors harbor qualifying alterations in FGFR2 or FGFR3. Currently, standard testing uses archival tumor tissue. However, this type of testing may not be representative of a patient's clinically dominant tumor clone at the time of treatment initiation due to temporal and spatial biopsy bias of archival tissue testing. In this study, patients will undergo circulating tumor DNA testing, in addition to conventional tissue testing, for treatment eligibility. Investigators hypothesize that blood-based ctDNA testing will provide a more accurate assessment of somatic FGFR status than same patient archival primary tissue. This study's objectives are: Objective 1 (Primary): To evaluate the diagnostic value of ctDNA testing against the gold standard of tissue testing. Objective 2 (Secondary): To evaluate whether ctDNA may be a superior predictive marker by identifying actionable FGFR alterations that are currently missed on tissue assays. Procedures: Medical history will be reviewed, including all previous anti-cancer treatments. A blood sample will be collected for ctDNA testing at the time of screening for FGFR alterations and at progression under erdafitinib therapy. Test results will be compared to archival tissue testing.

Official Title
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ctDNA-FGFR Status as a Predictive Biomarker for FGFR Targeted Therapy

Conditions
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Metastatic Bladder Cancer, Metastatic Urothelial Carcinoma

Intervention / Treatment
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* Genetic: FGFR Testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with metastatic bladder cancer who are about to undergo tissue testing for FGFR mutations and who have blood samples drawn during the management of their disease are eligible to be included in this analysis. Exclusion Criteria: Metastatic bladder cancer patients who will not have tissue sent for FGFR testing will be excluded from this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Metastatic Bladder Cancer<br>Patients with metastatic bladder cancer who will have archival tissue sent for FGFR testing. | Genetic: FGFR Testing<br>* Determine whether ctDNA testing for FGFR provides the same results as the standard tissue testing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the diagnostic value of ctDNA testing against standard tissue testing | Investigators will evaluate ctDNA as a diagnostic test against the de facto gold standard of tissue testing. | For the primary objective, a single blood sample is collected at the time of screening for treatment eligibility | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate whether ctDNA may be a superior predictive marker by identifying actionable FGFR mutations that are currently missed on tissue assays | To quantify the additional value of ctDNA testing, Investigators will calculate the percentage of eligible patients based on ctDNA testing among conventional testing ineligible or negative patients. | For this secondary objective, a single blood sample is collected at the time of screening for treatment eligibility | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ctDNA-FGFR, FGFR Biomarker, Erdafitinib