Study protocol of an open-label, single arm phase II trial investigating the efficacy and safety of Trifluridine/Tipiracil combined with irinotecan as a second line therapy in patients with cholangiocarcinoma (TRITICC)

Abstract

Background The prognosis of patients with advanced biliary tract cancer (BTC) who have progressed on gemcitabine plus cisplatin is dismal. Trifluridine/tipiracil (FTD/TPI) and irinotecan have proven efficacy in different gastrointestinal malignancies. We therefore hypothesized that this combination might improve the therapeutic outcome in patients with BTC after failure of first line treatment. Methods TRITICC is an interventional, prospective, open-label, non-randomised, exploratory, multicentre, single-arm phase IIA clinical trial done in 6 sites with expertise in managing biliary tract cancer across Germany. A total of 28 adult patients (aged ≥ 18 years) with histologically verified locally advanced or metastatic biliary tract cancer (including cholangiocarcinoma and gallbladder or ampullary carcinoma) with documented radiological disease progression to first-line gemcitabine based chemotherapy will be included to receive a combination of FTD/TPI plus irinotecan according to previously published protocols. Study treatment will be continued until disease progression according to RECIST 1.1 criteria or occurrence of unacceptable toxicity. The effect of FTD/TPI plus irinotecan on progression-free survival will be analyzed as primary endpoint. Safety (according to NCI-CTCAE), response rates and overall survival are secondary endpoints. In addition, a comprehensive translational research program is part of the study and might provide findings about predictive markers with regard to response, survival periods and resistance to treatment. Discussion The aim of TRITICC is to evaluate the safety and efficacy of FTD/TPI plus irinotecan in patients with biliary tract cancer refractory to previous Gemcitabine based treatment. Trial registration EudraCT 2018–002936-26; NCT04059562

New trends in diagnosis and management of gallbladder carcinoma

“…In cases of locally advanced or inoperable metastatic stage IV GB carcinoma, the addition of nab-paclitaxel to the standard gemcitabine-cisplatin treatment (GCNP scheme) as first-line therapy exhibited an increased response with potential resection after downstaging and prolonged survival[ 141 ]. Patients with resistance to gemcitabine-cisplatin as first-line therapy may benefit from second-line therapy with trifluridine-tipiracil and irinotecan[ 48 ].…”

“…Other management options include chemotherapy and radiotherapy, immunotherapy, and targeted therapy by monoclonal antibody biological agents[ 41 - 45 ]. The current rapidly evolving, multimodal therapeutic approach[ 46 ] and Medicaid expansion[ 47 ] have improved the results, opening new perspectives even in inoperable cases involving palliative treatment[ 4 , 13 , 48 - 50 ].…”