Journal Article

DKFZ-2026-00683

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png PROTECTOR / FIRE‑10: study protocol for a prospective, randomized, open-label, multicenter phase III trial to investigate the efficacy of preoperative systemic therapy in advanced colon cancer.

Siegel, R. ; Dittrich, L. ; Plewe, J. ; Denecke, T. ; Leonhardi, J. ; Tannapfel, A. ; Reinacher-Schick, A. ; Raschzok, N. ; Sauer, I. M. ; Lauscher, J. ; Lorenzen, S. ; Götze, T. ; Jelas, I. ; Stahler, A. ; Kurreck, A. ; Ballhausen, A. ; Ostendorf, B. N. ; Haase, O. ; Pratschke, J. ; Stintzing, S.DKFZ* ; Modest, D. P.DKFZ*

2026
BioMed Central London

Abstract: Background: Standard of care for non-metastatic colon cancer is surgeryfollowed by stage-guided adjuvant therapy and/or structured follow-up.Upfront surgery in resectable colon cancer is irrespective of local T/Nstage, whereas adjuvant systemic therapy is recommended according topathological staging. The role of neoadjuvant chemotherapy remainsunclear. Whereas perioperative systemic therapy in colon cancer seems tobe safe and may lead to pathologic downstaging, evidence on improvedsurvival and quality of life remains scarce. The PROTECTOR / FIRE‑10 trialaims to generate evidence that perioperative systemic therapy improvessurvival without compromising quality of life in locally advanced,mismatch-repair proficient colon cancer patients.Methods and Design:Open-label, randomized, controlled, multicenter, phase III study with twoparallel arms. Patients with locally advanced colon or upper rectal cancerstaged cT3-4 and/or cN+ are randomized in a 2:1 fashion (favoringpreoperative therapy) to investigate the efficacy, patient reported qualityof life, and safety of preoperative therapy followed by surgery (Arm A)versus direct surgery followed by non-study specific stage-guidedadjuvant therapy (Arm B). Stratification during randomization will beperformed according to the following parameters: Fit for mFOLFOXIRI vs.mFOLFOX/CAPOX vs. 80%-mFOLFOX/CAPOX, ECOG 0 vs. ECOG 1-2, andleft-sided primary vs. right-sided primary tumor. Only patients withconfirmed mismatch-repair proficient and/or microsatellite stable tumorcan be included.Preoperative treatment in Arm A is performed for a maximum of 6biweekly cycles of FOLFOX/FOLFOXIRI or for a maximum of 4 triweeklycycles CAPOX (i.e., appr. 12 weeks). Patients in both arms should undergoquality-controlled surgery of the primary tumor, performed as completemesocolic excision. Patients will be followed up with regard to relapse, survival and ifapplicable subsequent anti-cancer treatments until death or for at least 5years after randomization, whichever date is earlier.Discussion:The PROTECTOR / FIRE‑10 trial compares preoperative systemic therapyto upfront surgery (with stage-guided adjuvant therapy) in patients withlocally advanced colon cancer.

Keyword(s): Colon cancer ; Colorectal cancer ; Colorectal surgery ; Neoadjuvant therapy ; Preoperative chemotherapy

Note: #NCTZFB9# / epub

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Contributing Institute(s):

1. Koordinierungsstelle NCT Berlin (BR01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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