A Study to Compare the Results of FGFR Testing by Either ctDNA Blood Testing or Standard Tumor Tissue Testing
Study Details
Study Description
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, we will test the patient's blood for these genetic changes in addition to the tumor tissue samples. We think that the blood test will give a more accurate result.
We hope this study will help us to find out if more patients can benefit from erdafitinib than the ones identified by tissue testing only.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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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. We 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:
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Medical history will be reviewed, including all previous anti-cancer treatments.
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Metastatic Bladder Cancer Patients with metastatic bladder cancer who will have archival tissue sent for FGFR testing. |
Genetic: FGFR Testing
Determine whether ctDNA testing for FGFR provides the same results as the standard tissue testing.
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Outcome Measures
Primary Outcome Measures
- To evaluate the diagnostic value of ctDNA testing against standard tissue testing [For the primary objective, a single blood sample is collected at the time of screening for treatment eligibility]
We will evaluate ctDNA as a diagnostic test against the de facto gold standard of tissue testing.
Secondary Outcome Measures
- To evaluate whether ctDNA may be a superior predictive marker by identifying actionable FGFR mutations that are currently missed on tissue assays [For this secondary objective, a single blood sample is collected at the time of screening for treatment eligibility]
To quantify the additional value of ctDNA testing, we will calculate the percentage of eligible patients based on ctDNA testing among conventional testing ineligible or "negative" patients.
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tom Baker Cancer Centre | Calgary | Alberta | Canada | T2N 4N2 |
| 2 | Cross Cancer Institute | Edmonton | Alberta | Canada | T6G 1Z2 |
| 3 | BC Cancer Agency | Vancouver | British Columbia | Canada | V5Z 4E6 |
| 4 | London Health Sciences Centre | London | Ontario | Canada | N6A 5W9 |
| 5 | Ottawa Hospital Research Institute | Ottawa | Ontario | Canada | K1H 8L6 |
| 6 | Princess Margaret Cancer Centre | Toronto | Ontario | Canada | M5G 2M9 |
| 7 | CHU de Québec-Université Laval | Québec City | Quebec | Canada | G1R 2J6 |
Sponsors and Collaborators
- Bernie Eigl
- Vancouver Prostate Centre
- Lady Davis Institute
- Bladder Cancer Canada
Investigators
- Study Chair: Bernhard Eigl, British Columbia Cancer Agency
- Study Chair: Alexander Wyatt, Vancouver Prostate Centre
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- ctDNA FGFR