FIRE-9 – PORT / AIO-KRK-0418: a prospective, randomized, open, multicenter Phase III trial to investigate the efficacy of adjuvant/additive chemotherapy in patients with definitely-treated metastatic colorectal cancer
Nathanael Raschzok,
Sebastian Stintzing,
Volker Heinemann,
Geraldine Rauch,
Jens Ricke,
Matthias Guckenberger,
Annika Kurreck,
Annabel H. S. Alig,
Arndt Stahler,
Lars Bullinger,
Moritz Schmelzle,
Wenzel Schöning,
Georg Lurje,
Felix Krenzien,
Oliver Haase,
Beate Rau,
Bernhard Gebauer,
Igor M. Sauer,
Johann Pratschke,
Dominik P. Modest
Affiliations
Nathanael Raschzok
Department of Surgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Campus Charité Mitte | Campus Virchow-Klinikum
Sebastian Stintzing
Department of Hematoogy, Oncology, and Cancer Immunology (CCM/CVK), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin
Volker Heinemann
German Cancer Consortium, German Cancer Research Center
Geraldine Rauch
Institute of Biometry and Clinical Epidemiology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin
Jens Ricke
Department of Radiology, LMU University Hospital
Matthias Guckenberger
Department for Radiation Oncology, University Hospital Zurich, University of Zurich
Annika Kurreck
Department of Hematoogy, Oncology, and Cancer Immunology (CCM/CVK), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin
Annabel H. S. Alig
Department of Hematoogy, Oncology, and Cancer Immunology (CCM/CVK), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin
Arndt Stahler
Department of Hematoogy, Oncology, and Cancer Immunology (CCM/CVK), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin
Lars Bullinger
Department of Hematoogy, Oncology, and Cancer Immunology (CCM/CVK), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin
Moritz Schmelzle
Department of Surgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Campus Charité Mitte | Campus Virchow-Klinikum
Wenzel Schöning
Department of Surgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Campus Charité Mitte | Campus Virchow-Klinikum
Georg Lurje
Department of Surgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Campus Charité Mitte | Campus Virchow-Klinikum
Felix Krenzien
Department of Surgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Campus Charité Mitte | Campus Virchow-Klinikum
Oliver Haase
Department of Surgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Campus Charité Mitte | Campus Virchow-Klinikum
Beate Rau
Department of Surgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Campus Charité Mitte | Campus Virchow-Klinikum
Bernhard Gebauer
Department of Radiology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin
Igor M. Sauer
Department of Surgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Campus Charité Mitte | Campus Virchow-Klinikum
Johann Pratschke
Department of Surgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Campus Charité Mitte | Campus Virchow-Klinikum
Dominik P. Modest
Department of Hematoogy, Oncology, and Cancer Immunology (CCM/CVK), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin
Abstract Background Additive/adjuvant chemotherapy as concept after local treatment of colorectal metastases has not been proven to be successful by phase III trials. Accordingly, a standard of care to improve relapse rates and long-term survival is not established and adjuvant chemotherapy cannot be recommended as a standard therapy due to limited evidence in literature. The PORT trial aims to generate evidence that post-resection/ablation/radiation chemotherapy improves the survival in patients with metastatic colorectal cancer. Methods Patients to be included into this trial must have synchronous or metachronous metastases of colorectal cancer—either resected (R0 or R1) and/or effectively treated by ablation or radiation within 3–10 weeks before randomization—and have the primary tumor resected, without radiographic evidence of active metastatic disease at study entry. The primary endpoint of the trial is progression-free survival after 24 months, secondary endpoints include overall survival, safety, quality of life, treatments (including efficacy) beyond study participation, translational endpoints, and others. One arm of the study comprising 2/3 of the population will be treated for 6 months with modified FOLFOXIRI or modified FOLFOX6 (investigator´s choice, depending on the performance status of the patients but determined before randomization), while the other arm (1/3 of the population) will be observed and undergo scheduled follow-up computed tomography scans according to the interventional arm. Discussion Optimal oncological management after removal of colorectal metastases is unclear. The PORT trial aims to generate evidence that additive/adjuvant chemotherapy after definitive treatment of colorectal metastases improves progression free and overall survival in patients with colorectal cancer. Trial registration This study is registered with clinicaltrials.gov ( NCT05008809 ) and EudraCT (2020–006,144-18).
