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, 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

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).

Keywords: Adjuvant chemotherapy; Colorectal cancer; Colorectal metastases.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

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Fig. 1
Trial design
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Fig. 2
Study visits

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