Detection of FGFR Gene Mutations in the Tumor Tissue and Urine of Patients With Urothelial Carcinoma

This study aims to compare the correlation between FGFR mutations found in bladder cancer tissues and urine to develop a companion diagnostic method for predicting the effect of FGFR inhibitors using urine samples of the patients with urothelial cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Diagnostic test: FGFR test

Detailed Description

This study targets 92 patients with urothelial cancer, whose tissue (from scheduled surgery) and urine samples can be obtained, regardless of the treatment stage.

■ Examination Methods

• FGFR mutations in bladder cancer tissues will be analyzed using next-generation sequencing and current companion diagnostic methods.
• FGFR mutations in urine samples obtained from patients with bladder cancer will be analyzed using nanowires.
• Bladder cancer subtyping will be performed by RNA sequencing of tumor tissues or other methods.
• Analysis of paired tissues before and after chemotherapy will be performed on transurethral resection of bladder tumor (TUR-BT) and cystectomy tissues before and after neoadjuvant chemotherapy.

• Study Type: Observational
• Enrollment (Anticipated): 92

Contacts and Locations

• Study Contact: Name: Ho Kyung Seo, MD, PhD; Phone Number: +82-31-920-1678; Email: seohk@ncc.re.kr
• Study Contact Backup: Name: Sahyun Pak, MD; Phone Number: +82-31-920-2794; Email: sahyun@ncc.re.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Suspected patients of urothelial cancer who will visit the National Cancer Center Korea.

Description

Inclusion Criteria:

• Suspected patients of urothelial cancer who will visit the National Cancer Center Korea from the date of Institutional Review Board (IRB) approval to 2021 and with identified tumors in the bladder according to bladder endoscopy.
• Subjects who are scheduled for surgery (transurethral bladder tumor resection, radical bladder resection, and radical bladder ureterectomy) and have agreed to participate in the study

Exclusion Criteria:

• History of other active malignant tumors treated within 24 months
• Patients with either mental illness or who cannot participate in clinical trials at the judgment of other doctors
• If patients and guardians do not want to participate in this study
• History of having administered FGFR inhibitors in the past

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
BC; Patients who were diagnosed with bladder cancer	Diagnostic test: FGFR test; Detection of FGFR gene mutations in the tumor tissue and urine of patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between FGFR mutations found in bladder cancer tissues and urine before and after treatment	The ratio of patients with matching test results to total patients	Up to two weeks before and after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in FGFR mutations in tissues before and after treatment	Changes in FGFR mutations in tissues before and after treatment will be observed in the patients with muscle-invasive and non-muscle-invasive bladder cancer undergoing neoadjuvant chemotherapy and transurethral bladder tumor resection, respectively, due to recurrence.	Up to two weeks before and after treatment
Patient prognosis	recurrence-free	six months and one year after treatment
Patient prognosis	progression-free	six months and one year after treatment
Patient prognosis	cancer-specific survivals	six months and one year after treatment
Patient prognosis	overall survivals	six months and one year after treatment
PD-L1 expression	PD-L1 expression level will be measured using immunohistochemistry, RNA sequencing, and other suitable methods to analyze the bladder cancer subtypes	Up to two weeks before and after treatment

Collaborators and Investigators

• Sponsor: Ho Kyung Seo
• Investigators: Principal Investigator: Ho Kyung Seo, MD, PhD, National Cancer Center, Korea

Publications and helpful links

General Publications

• Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014 Mar 20;507(7492):315-22. doi: 10.1038/nature12965. Epub 2014 Jan 29.
• Loriot Y, Necchi A, Park SH, Garcia-Donas J, Huddart R, Burgess E, Fleming M, Rezazadeh A, Mellado B, Varlamov S, Joshi M, Duran I, Tagawa ST, Zakharia Y, Zhong B, Stuyckens K, Santiago-Walker A, De Porre P, O'Hagan A, Avadhani A, Siefker-Radtke AO; BLC2001 Study Group. Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2019 Jul 25;381(4):338-348. doi: 10.1056/NEJMoa1817323.
• Wu YM, Su F, Kalyana-Sundaram S, Khazanov N, Ateeq B, Cao X, Lonigro RJ, Vats P, Wang R, Lin SF, Cheng AJ, Kunju LP, Siddiqui J, Tomlins SA, Wyngaard P, Sadis S, Roychowdhury S, Hussain MH, Feng FY, Zalupski MM, Talpaz M, Pienta KJ, Rhodes DR, Robinson DR, Chinnaiyan AM. Identification of targetable FGFR gene fusions in diverse cancers. Cancer Discov. 2013 Jun;3(6):636-47. doi: 10.1158/2159-8290.CD-13-0050. Epub 2013 Apr 4.

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2022
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): March 31, 2025

Study Registration Dates

• First Submitted: April 7, 2020
• First Submitted That Met QC Criteria: April 8, 2020
• First Posted (Actual): April 9, 2020

Study Record Updates

• Last Update Posted (Actual): April 7, 2022
• Last Update Submitted That Met QC Criteria: April 6, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Carcinoma, Transitional Cell
• Other Study ID Numbers: U-FGFR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No