CWoW - The PROOF Trial
Research type
Research Study
Full title
A Phase 3 Multicenter, Open-Label, Randomized, Controlled Study of Oral Infigratinib versus Gemcitabine with Cisplatin in Subjects with Advanced/Metastatic or Inoperable Cholangiocarcinoma with FGFR2 Gene Fusions/Translocations: The PROOF Trial
IRAS ID
265626
Contact name
Juan Valle
Contact email
Sponsor organisation
QED Therapeutics, Inc.
Eudract number
2018-004004-19
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
US IND Number, 104187
Duration of Study in the UK
5 years, 0 months, 0 days
Research summary
This is an open-label comparator-controlled Phase 3 study to see how effective the experimental drug infigratinib is in patients with advanced, metastatic or inoperable cholangiocarcinoma when compared to the standard of care treatment of intravenous gemcitabine and cisplatin.
Cholangiocarcinoma is the most common biliary tract cancer with approximately 1,000 new cases diagnosed in the UK between 2014-2016. Cholangiocarcinoma is an aggressive disease and due to its lack of /late emergence of symptoms, it is often not diagnosed until an advanced stage. This contributes to the poor outcomes and high mortality rate associated with the disease.
For patients who can’t undergo surgical treatment, current treatments include gemcitabine and cisplatin, a non-specific therapy that can significantly increase progression free survival, and local therapies (e.g. radiotherapy), which have limited effect on survival. Due to the lack of targeted treatments for cholangiocarcinoma, there is a real need to develop novel therapeutics based on specific molecular targets that can significantly improve clinical outcomes. In particular, genetic alterations involving the fibroblast growth factor receptor (FGFR) family could be an important target for treatment of cholangiocarcinoma.
Infigratinib, the study drug, blocks FGFRs 1-3, which are involved in cell growth and blood vessel development. Inappropriate FGFR activity plays an important role in the development of cholangiocarcinoma, and mutations in the FGFRs have been found in about 16% of cases. Recent Phase 1 and 2 studies have identified no significant safety risks to date.
Approximately 350 patients with cholangiocarcinoma will be enrolled during the trial, half of which will be randomised to receive infigratinib, and the other half gemcitabine and cisplatin. Study assessments will include blood and urine sampling, vital signs, ECG, ECHO/MUGA scans, CT/MRI scans, ophthalmic assessments, physical examinations and questionnaires, as well as monitoring of adverse events and existing treatments.
REC name
North West - Haydock Research Ethics Committee
REC reference
20/NW/0134
Date of REC Opinion
21 Apr 2020
REC opinion
Further Information Favourable Opinion