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

Metastatic Urothelial Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06129084
• Other study ID #: ctDNA FGFR
• Status: Recruiting
• Start date: January 11, 2021
• Est. completion date: June 1, 2024

Study information

• Verified date: November 2023
• Source: British Columbia Cancer Agency
• Contact: Clinical Research and Trials Coordinator
• Phone: 604-877-6000
• Email: lisa.rebane[@]bccancer.bc.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 210
• Est. completion date: June 1, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Transitional Cell
• Metastatic Bladder Cancer
• Metastatic Urothelial Carcinoma

Intervention

Genetic:
• FGFR Testing
Determine whether ctDNA testing for FGFR provides the same results as the standard tissue testing.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	CHU de Québec-Université Laval	Québec City	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	BC Cancer Agency	Vancouver	British Columbia

Sponsors (4)

Lead Sponsor	Collaborator
Bernie Eigl	Bladder Cancer Canada, Lady Davis Institute, Vancouver Prostate Centre

Country where clinical trial is conducted

Canada, 

References & Publications (2)

Knowles MA, Hurst CD. Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity. Nat Rev Cancer. 2015 Jan;15(1):25-41. doi: 10.1038/nrc3817. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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