Study protocol: a phase II study of trifluridine/tipiracil plus liposomal irinotecan as second-line therapy in advanced biliary tract cancer (TRITICC 2)

BMC Cancer, vol. 26

Abstract

BACKGROUND: The prognosis of patients with advanced biliary tract cancer progressing after gemcitabine-based first-line therapy remains poor. Effective second-line treatment options are limited, and outcomes with currently available regimens are modest. Trifluridine/tipiracil (FTD/TPI) and nanoliposomal irinotecan (nal-IRI) have demonstrated clinical activity in gastrointestinal malignancies and may provide synergistic antitumor effects. METHODS: TRITICC-2 is an investigator-initiated, prospective, open-label, multicenter, single-arm phase II trial conducted at academic centers in Germany. The study evaluates the efficacy and safety of FTD/TPI in combination with nal-IRI in patients with histologically confirmed, unresectable or metastatic biliary tract cancer who have progressed on gemcitabine-based first-line therapy. A total of 38 patients are planned for enrollment. Treatment consists of oral FTD/TPI administered on days 1-5 combined with intravenous nal-IRI on day 1 of a 14-day cycle, continued until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), objective response rate (ORR), safety, and health-related quality of life. An optional translational research program includes serial liquid biopsies and biomarker analyses. Enrollment is ongoing, with recruitment initiated in late 2025. Efficacy, safety, and translational analyses are pending. CONCLUSION: TRITICC-2 investigates a biologically rational combination of FTD/TPI and nal-IRI in a patient population with a high unmet medical need. The study is expected to provide prospective data on the clinical activity and safety of this regimen and may contribute to the identification of biomarkers associated with treatment response in advanced biliary tract cancer. TRIAL REGISTRATION: EUCT 2024-517330-18-00.

Authors 13

1. Linde Kehmann

   Servier (Germany) · Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Campus Virchow Klinikum, 13353, Berlin, Germany

   Servier Deutschland GmbH, 80687, München, Germany

2. Thorsten Götze

   Goethe University Frankfurt · Institute of Clinical Cancer Research · University Hospital Frankfurt · Frankfurt Cancer Institute

   Affiliation as printed

   Hospital Northwest, University Cancer Center Frankfurt, 60488, Frankfurt, Germany

   The Frankfurt Institute of Clinical Cancer Research IKF GmbH, 60488, Frankfurt, Germany

3. Maria Gonzalez-Carmona

   University Hospital Bonn

   Affiliation as printed

   Department of Internal Medicine I, University Hospital of Bonn, 53127, Bonn, Germany

4. F Foerster

   Johannes Gutenberg University Mainz · University Medical Center of the Johannes Gutenberg University Mainz

   Affiliation as printed

   Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg University Mainz, 55131, Mainz, Germany

5. Marie Berres Aachen Medical Department III

   Integrated Oncology (United States) · Universitätsklinikum Aachen

   Affiliation as printed

   Center for Integrated Oncology - Aachen Bonn Cologne Duesseldorf (CIO-ABCD), 52074, Aachen, Germany

   Medical Department III, University Hospital of Aachen, 52074, Aachen, Germany

6. Raphael Mohr

   Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Campus Virchow Klinikum, 13353, Berlin, Germany

7. Alexander Koch Aachen Medical Department III

   Integrated Oncology (United States) · Universitätsklinikum Aachen

   Affiliation as printed

   Center for Integrated Oncology - Aachen Bonn Cologne Duesseldorf (CIO-ABCD), 52074, Aachen, Germany

   Medical Department III, University Hospital of Aachen, 52074, Aachen, Germany

8. Samayita Das

   Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Campus Virchow Klinikum, 13353, Berlin, Germany

9. Nadja Drusenheimer

   Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Coordination Center for Clinical Trials, Medical Faculty, University Hospital Duesseldorf, Heinrich Heine - University, 40225, Duesseldorf, Germany

10. Tewodros Kebede

    Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

    Affiliation as printed

    Coordination Center for Clinical Trials, Medical Faculty, University Hospital Duesseldorf, Heinrich Heine - University, 40225, Duesseldorf, Germany

11. Markus Sebastian Jördens

    Düsseldorf University Hospital · Integrated Oncology (United States) · Heinrich Heine University Düsseldorf

    Affiliation as printed

    Center for Integrated Oncology - Aachen Bonn Cologne Duesseldorf (CIO-ABCD), 40225, Duesseldorf, Germany

    Clinic for Gastroenterology, Hepatology & Infectious Diseases, University Hospital of Düsseldorf, 40225, Düsseldorf, Germany

12. Tom Luedde

    Düsseldorf University Hospital · Integrated Oncology (United States) · Heinrich Heine University Düsseldorf

    Affiliation as printed

    Center for Integrated Oncology - Aachen Bonn Cologne Duesseldorf (CIO-ABCD), 40225, Duesseldorf, Germany

    Clinic for Gastroenterology, Hepatology & Infectious Diseases, University Hospital of Düsseldorf, 40225, Düsseldorf, Germany

13. Christoph Roderburg corresponding

    Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

    Affiliation as printed

    Center for Integrated Oncology - Aachen Bonn Cologne Duesseldorf (CIO-ABCD), 40225, Duesseldorf, Germany. christoph.roderburg@med.uni-duesseldorf.de

    Clinic for Gastroenterology, Hepatology & Infectious Diseases, University Hospital of Düsseldorf, 40225, Düsseldorf, Germany. christoph.roderburg@med.uni-duesseldorf.de