PROOF 302
Research type
Research Study
Full title
Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of Infigratinib for the Adjuvant Treatment of Subjects with Invasive Urothelial Carcinoma with Susceptible FGFR3 Genetic Alterations (PROOF 302)
IRAS ID
273772
Contact name
Deborah Enting
Contact email
Sponsor organisation
QED Therapeutics, Inc.
Eudract number
2019-003248-63
Clinicaltrials.gov Identifier
144,007, US IND Number
Duration of Study in the UK
5 years, 0 months, 25 days
Research summary
Research Summary:
This research study is looking at the effects of the medication, infigratinib, in patients with invasive urothelial carcinoma (cancer of the bladder or cancer of the upper urinary tract) following surgical removal of the cancer.
Upper Tract Urothelial Carcinoma (UTUC) comprises approximately 5% to 10% of all urothelial carcinomas and occurs mostly in 70-90 year old patients. At the time of diagnosis, 60% of UTUC patients have invasive cancer and 28% have recurrence outside of the bladder after surgical removal. Furthermore, approximately 20% of patients with urothelial carcinoma have invasive Urinary Bladder Cancer (UBC) at the time of diagnosis.
It is thought that an abnormal change in the Fibroblast Growth Factor Receptor 3 (FGFR3) gene may be involved in both UTUC and UBC, causing cells to grow uncontrollably and develop into cancer. It is hoped that infigratinib will stop the abnormal FGFR3 gene from causing cells to grow uncontrollably. Participants will receive either infigratinib or placebo (dummy medication) to determine if those who receive infigratinib for one year will remain cancer-free compared with those who receive a placebo for one year.
Patients may be eligible for participation if they meet the study criteria e.g. are confirmed to have the abnormal FGFR3 gene, and had their cancer surgically removed.
Approximately 218 participants are expected to be enrolled in the study at around 120 study sites in the UK and worldwide. Participants will be asked to complete 1 to 5 visits per month until they are no longer taking the study medication. Their participation will last for approximately 4 years, although this may change depending on their response to the study medication and how long other participants remain in the study.
Summary of Results:
On 05 October 2022, Helsinn Healthcare SA (HCC) made a business decision to discontinue development and commercialization of TRUSELTIQ™ (Infigratinib). As a result of this decision, new drug and marketing authorisation applications worldwide were withdrawn and the further development of Infigratinib in oncology outside of China was terminated. This event subsequently led to the closure of this study. The decision to stop development of Infigratinib in the oncology setting was not made based on any efficacy or safety concerns. At the time of the decision to terminate the study early, only 39 participants were enrolled, which rendered the study futile. Consequently, no statistical testing could be done. At the time of decision to terminate the study early, no participants were receiving treatment in the UK.
With only 39 patients randomised, the number of Disease Free Survival (DFS) events required to assess efficacy objectives was not nearly achieved. With the limited data, the study cannot establish a positive risk benefit in the treatment of urothelial carcinoma. Data on safety and tolerability contribute towards further characterisation of the safety profile of Infigratinib.
During the trial, the Sponsor become aware of participants in the US, Puerto Rico and Spain, with hepatic or renal impairment receiving a dose higher than recommended. This was classified as a serious breach, and was notified to ethics committees. The serious breach did not qualify as an urgent safety measure, as there were no serious adverse effects related to the higher starting dose. There was no subsequent impact on the trial analysis or results, as the study was terminated early, and no statistical testing was completed.
This summary shows only the main results from this one study. You can find more information about this study on the websites listed below.
https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C01%7Coxforda.rec%40hra.nhs.uk%7C9985b99205884a3e7a7808dbd1675f9f%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638334014147706921%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=3KPYNrJ1uMXogkcN2eA20D48apvu7dqehKFYJuUI5pY%3D&reserved=0 and search NCT04197986
https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C01%7Coxforda.rec%40hra.nhs.uk%7C9985b99205884a3e7a7808dbd1675f9f%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638334014147706921%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=XuZBc%2FJGyfiVn%2B2x6JgiHo7QMrp40qO0pFkExXl4Xj8%3D&reserved=0 and search 2019-003248-63REC name
South Central - Oxford A Research Ethics Committee
REC reference
20/SC/0046
Date of REC Opinion
4 May 2020
REC opinion
Further Information Favourable Opinion