Clinical trial NCT06129084: A Study to Compare the Results of FGFR Testing by Either CtDNA Blood Testing or Standard Tumor Tissue Testing
Official title: CtDNA-FGFR Status As a Predictive Biomarker for FGFR Targeted Therapy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Metastatic Bladder Cancer
Metastatic Urothelial Carcinoma
Keywords: ctDNA-FGFR
FGFR Biomarker
Erdafitinib
Lead sponsor: British Columbia Cancer Agency
Sponsor class: OTHER
Collaborators: name: Vancouver Prostate Centre
name: Lady Davis Institute
name: Bladder Cancer Canada
First posted: 2023-11-13
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with metastatic urothelial cancer who are screened for erdafitinib eligibility as standard of care.

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: To evaluate the diagnostic value of ctDNA testing against standard tissue testing
timeFrame: For the primary objective, a single blood sample is collected at the time of screening for treatment eligibility
Secondary outcomes:
measure: To evaluate whether ctDNA may be a superior predictive marker by identifying actionable FGFR mutations that are currently missed on tissue assays
timeFrame: For this secondary objective, a single blood sample is collected at the time of screening for treatment eligibility
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Arthur J.E Child Comprehensive Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer Agency
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Québec City
country: Canada
facility: CHU de Québec-Université Laval
state: Quebec
Study officials:
affiliation: British Columbia Cancer Agency
name: Bernhard Eigl
role: STUDY_CHAIR
affiliation: Vancouver Prostate Centre
name: Alexander Wyatt
role: STUDY_CHAIR
References:
citation: 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.
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.