Post-resection/Ablation Chemotherapy in Patients With Metastatic Colorectal Cancer (FIRE-9 - PORT / AIO-KRK-0418)
NCT ID: NCT05008809
Last Updated: 2025-12-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE3
507 participants
INTERVENTIONAL
2021-12-06
2030-11-30
Brief Summary
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Detailed Description
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The objective of the re-assessments is detection of relapse either radiologically or within the translational material (blood samples with ctDNA dynamics and tumor - if available from relapses). CT scans of thorax/abdomen and/or MRI scans will be performed every 3 months within the 2 years after randomization. After the first two relapse-free years, intervals should be stretched to 6 months in the third and following years after study start. Structured follow-up for up to 60 months after randomization should be maintained for both arms.
Patients in Arm A receive additive study drug intervention (mFOLFOXIRI or mFOLFOX-6) for up to six months (12 cycles) after randomization with additional clinical and safety assessments.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Treatment
Active treatment with mFOLFOXIRI or mFOLFOX6 or FOLFIRI q2w or CAPOX q3w up to six months followed by structured Follow-up for up to five years after randomization
mFOLFOX6
Oxaliplatin: 85 mg/m², 2h IV infusion on d1 Folinic acid: 400 mg/m², 1-2 h IV infusion on d1 5-FU: (optional: 400 mg/m² bolus, 2-5 min IV infusion), 2400 mg/m², 46 h IV infusion on d1 Cycles are repeated on day 15. A total of up to 12 cycles are administered.
mFOLFOXIRI
Oxaliplatin: 85 mg/m², 2h IV infusion on d1 Irinotecan: 150 mg/m², 90 min IV infusion on d1 Folinic acid: 400 mg/m², 1-2 h IV infusion on d1 5-FU: 2400 mg/m², 46 h IV infusion on d1 Cycles are repeated on day 15. A total of up to 12 cycles are administered.
FOLFIRI
Folinic acid: 400mg/m², 1-2h IV Infusion on d1 5-FU: 2400 mg/m², 46 h IV infusion on d1 Irinotecan: 180 mg/m², 90-120 min IV infusion on d1 Cycles are repeated on day 15. A total of up to 12 cycles is administered.
CAPOX
Capecitabine: 1000 mg/m², oral 1-0-1 on d1-14 Oxaliplatin: 130 mg/m², 3h IV infusion on d1 Cycles are repeated on day 22. A total of up to 8 cycles isadministered.
Control
Structured Follow-up for up to five years after randomization
No interventions assigned to this group
Interventions
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mFOLFOX6
Oxaliplatin: 85 mg/m², 2h IV infusion on d1 Folinic acid: 400 mg/m², 1-2 h IV infusion on d1 5-FU: (optional: 400 mg/m² bolus, 2-5 min IV infusion), 2400 mg/m², 46 h IV infusion on d1 Cycles are repeated on day 15. A total of up to 12 cycles are administered.
mFOLFOXIRI
Oxaliplatin: 85 mg/m², 2h IV infusion on d1 Irinotecan: 150 mg/m², 90 min IV infusion on d1 Folinic acid: 400 mg/m², 1-2 h IV infusion on d1 5-FU: 2400 mg/m², 46 h IV infusion on d1 Cycles are repeated on day 15. A total of up to 12 cycles are administered.
FOLFIRI
Folinic acid: 400mg/m², 1-2h IV Infusion on d1 5-FU: 2400 mg/m², 46 h IV infusion on d1 Irinotecan: 180 mg/m², 90-120 min IV infusion on d1 Cycles are repeated on day 15. A total of up to 12 cycles is administered.
CAPOX
Capecitabine: 1000 mg/m², oral 1-0-1 on d1-14 Oxaliplatin: 130 mg/m², 3h IV infusion on d1 Cycles are repeated on day 22. A total of up to 8 cycles isadministered.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Patient's age ≥18 years at the time of signing the informed consent.
3. Histologically confirmed adenocarcinoma of the colon or rectum.
4. Resected (R0 or R1) and/or effectively treated metastases (all techniques allowed) of colorectal cancer within 3-10 weeks before randomization (earlier randomisation allowed if at least 3 weeks interval between intervention and treatment start is guaranteed) AND resected primary tumor (synchronous or metachronous). In cases of synchronous metastases the interval of 3-10 weeks might be calculated following the removal of the primary tumor if this intervention was the last to address all tumor lesions.
5. Absence of significant active wound healing complications (if applicable) at randomization. Resolved wound healing complications after resection/ablation are acceptable for inclusion into the trial.
6. No radiographic evidence of active metastatic disease at study entry in a CT and/or MRI scan not older than 10 weeks prior randomization. Pre-surgery/ablation images are eligible for the study if all lesions have been addressed in the interval.
7. ECOG performance status 0-2.
8. Adequate bone marrow, hepatic and renal organ function, defined by the following laboratory test results:
* Absolute neutrophil count \>= 1.5 x 109/L (1500/µL)
* Hemoglobin ≥ 80 g/L (8 g/dL)
* Platelet count ≥ 100 x109/L (100000/µL) without transfusion
* Total serum bilirubin of ≤ 1.5 x upper limit of normal (ULN)
* Aspartate aminotransferase (AST/GOT) ≤ 3.0 × ULN.
* Calculated glomerular filtration rate (GFR) according to Cockcroft-Gault formula or according to MDRD ≥ 50 mL/min or serum creatinine ≤ 1.5 x ULN
9. Patients without anticoagulation need to present with an INR \< 1.5 x ULN and PTT \< 1.5 x ULN. Patient with prophylactic or therapeutic anticoagulation are allowed into the trial.
10. Proficient fluorouracil metabolism as defined:
1. Prior treatment with 5-FU or capecitabine without unusual toxicity or
2. If tested, normal DPD deficiency test according to the standard of the study site or
3. If tested, in patients with DPD deficiency test with a CPIC activity score of 1.0-1.5 fluoropyrimidine/capecitabine dosage should be reduced by 50%
11. For women of childbearing potential (WOCBP): negative pregnancy test within 14 days before randomization and agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for at least 9 months after the last dose of Oxaliplatin or for at least 6 months after the last dose of all other study treatment.
A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male partner's sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
For men: With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year during the treatment period and for 6 months after the last dose of study treatment. Men must refrain from donating sperm during this same period.
Exclusion Criteria
2. Treatment of metastases greater than 5 cm with radiation (stereotactic/ brachytherapy) within 24 months prior to study entry if applicable.
3. Any previous systemic therapy is allowed for inclusion into the trial. However, if previous oxaliplatin-containing chemotherapy at any time for metastatic or localized disease was carried out, the inclusion into the trial is permitted under the condition, that
1. A total duration of oxaliplatin-based therapy of six months (i.e. 12 cycles of FOLFOX / FOLFOXIRI or 8 cycles CAPOX) is not exceeded - including therapy within the FIRE-9/PORT trial
2. If already more than three months of oxaliplatin-based therapy (i.e. \>6 cycles of FOLFOX / FOLFOXIRI or \>4 cycles CAPOX) was used, the study therapy should be started with an irinotecan-based regimen (i.e. FOLFIRI or FOLFOXIRI) However, in the case of FOLFOXIRI therapy in the trial, the above mention regulation concerning the total dosing of oxaliplatin still applies (i.e. 12 cycles of FOLFOX / FOLFOXIRI or 8 cycles CAPOX should not be exceeded - including therapy within the FIRE-9/PORT trial).
4. New York Heart Association Class III or greater heart failure by clinical judgement.
5. Myocardial infarction within 6 months prior to randomization; percutaneous transluminal coronary angioplasty (PTCA) with or without stenting within 6 months prior to randomization.
6. Unstable angina pectoris.
7. Unstable cardiac arrhythmia \> grade 2 NCI CTCAE despite anti-arrhythmic therapy.
8. Ongoing toxicities \> grade 2 NCI CTCAE
9. Active uncontrolled infection by investigator's perspective.
10. Severe chronic non-healing wounds, ulcerous lesions or untreated bone fracture.
11. Known hypersensitivity to 5-FU, folinic acid, irinotecan, oxaliplatin or capecitabine or to any of the other excipients listed in section 6.1 of the corresponding SmPC.
12. Recent or concomitant treatment with brivudine.
13. Peripheral sensitive neuropathy with functional impairment (\> grade 1 acc. to CTCAE version 5.0 (see appendix 2)).
14. Inflammatory bowel disease and/or bowel obstruction.
15. Simultaneous application of Johannis herbs preparations.
16. Pernicious or other megaloblastic anemia caused by vitamin B12 deficiency.
17. Major surgical procedure, open biopsy, or significant traumatic injury within 21 days prior to randomization or at least to intended treatment start, or anticipation of need for major surgical procedure during the course of the study or non-recovery from side effects of any such procedure.
18. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications.
19. Medical history of malignant disease other than mCRC with the following exceptions:
* patients who have been disease-free for at least three years before randomization
* patients with adequately treated and completely resected basal cell or squamous cell skin cancer, in situ cervical, breast or prostate cancer, stage I uterine cancer
* patients with any treated or untreated malignant disease that is associated with a 5-year survival prognosis of ≥ 90% and does not require active therapy
20. Known alcohol or drug abuse.
21. Pregnant or breastfeeding females.
22. Participation in a clinical trial or experimental drug treatment within 28 days prior to potential inclusion in the clinical trial or within a period of 5 half-lives of the substances administered in a clinical trial or during an experimental drug treatment prior to potential inclusion in the clinical trial, depending on which period is longest, or simultaneous participation in another clinical trial while taking part in this clinical trial.
23. Patients depending on Sponsor, investigator or study site.
24. Suspected SARS-CoV-2 infection with or without symptoms (evaluation according to local policy in respective center with respect to actual status of pandemic and with reference to the policy that would apply to patients with similar therapy outside the trial). This may include assessment of vaccination status, anamnesis, physical examination and potentially antigen and/or PCR testing.
25. Patient committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
26. Limited legal capacity.
27. Concomitant administration of strong CYP3A4 and/or UGT1A1 inducers (e.g. Rifampicin, Carbamazepin, Phenobarbital, Phenytoin or Apalutamid).
28. Planned inoculation/vaccination with a live vaccine during treatment with Oxaliplatin and/or Irinotecan, and until 6 months after treatment with Irinotecan.
18 Years
ALL
No
Sponsors
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Dominik Paul Modest
OTHER
German Research Foundation
OTHER
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
OTHER
Responsible Party
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Dominik Paul Modest
Prof. Dr. med.
Principal Investigators
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Dominik Modest, Prof. Dr.
Role: PRINCIPAL_INVESTIGATOR
Charite University, Berlin, Germany
Locations
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München Klinik Bogenhausen
München, , Germany
München Klinik Neuperlach
München, , Germany
Gemeinschaftspraxis Münster
Münster, , Germany
Universitätsklinikum Münster
Münster, , Germany
Klinikum St. Marien Amberg
Amberg, , Germany
Helios Klinikum Bad Saarow
Bad Saarow, , Germany
Klinikum Bayreuth
Bayreuth, , Germany
Charité Universitätsmedizin Berlin
Berlin, , Germany
Helios Klinikum Emil von Behring
Berlin, , Germany
MVZ Onkologischer Schwerpunkt am Oskar-Helene-Heim
Berlin, , Germany
Vivantes Klinikum am Urban Berlin
Berlin, , Germany
Vivantes Klinikum Spandau Berlin
Berlin, , Germany
St. Josef-Hospital Bochum
Bochum, , Germany
Johanniterkrankenhaus Bonn
Bonn, , Germany
Diakonie-Krankenhaus Bremen
Bremen, , Germany
Klinikum Chemnitz
Chemnitz, , Germany
Kliniken der Satdt Köln
Cologne, , Germany
Klinikum Darmstadt
Darmstadt, , Germany
DONAUISAR Klinikum Deggendorf
Deggendorf, , Germany
Städtisches Klinikum Dessau
Dessau, , Germany
Onkologische-Gemeinschaftspraxis Dresden
Dresden, , Germany
Onkozentrum Dresden
Dresden, , Germany
Universitätsklinikum Düsseldorf
Düsseldorf, , Germany
Kliniken Essen-Mitte
Essen, , Germany
Universitätsklinikum Essen
Essen, , Germany
KHNW Frankfurt
Frankfurt, , Germany
Markus-Krankenhaus Frankfurt
Frankfurt, , Germany
Universitätsklinikum Frankfurt
Frankfurt, , Germany
Universitätsklinikum Freiburg
Freiburg im Breisgau, , Germany
Gemeinschaftspraxis internistische Onkologie Fürth
Fürth, , Germany
Niels-Stensen Kliniken Georgsmarienhütte
Georgsmarienhütte, , Germany
Praxis Hämatologie Onkologie Gießen
Giessen, , Germany
Universitätsmedizin Göttingen
Göttingen, , Germany
Universitätsklinikum Halle
Halle, , Germany
Universitätsklinikum Hamburg-Eppendorf
Hamburg, , Germany
Medizinische Hochschule Hannover
Hanover, , Germany
St. Anna Hospital Herne
Herne, , Germany
Universitätsklinikum des Saarlandes
Homburg, , Germany
Klinikum Ingolstadt GmbH
Ingolstadt, , Germany
Universitätsklinikum Jena
Jena, , Germany
Klinikum Landshut
Landshut, , Germany
VK&K Studien Landshut
Landshut, , Germany
Studienzentrum UnterEms Leer
Leer, , Germany
Universitätsklinikum Leipzig
Leipzig, , Germany
Klinikum Leverkusen
Leverkusen, , Germany
Klinikum Lippe
Lippe, , Germany
Klinikum Ludwigsburg
Ludwigsburg, , Germany
Klinikum Magdeburg
Magdeburg, , Germany
Universitätsmedizin Mainz
Mainz, , Germany
OnkoNet Marburg GmbH
Marburg, , Germany
Philipps-Universität Marburg
Marburg, , Germany
Johannes Wesling Klinikum Minden
Minden, , Germany
Kliniken Maria Hilf Mönchengladbach
Mönchengladbach, , Germany
Klinikum der Universität München
München, , Germany
Klinikum rechts der Isar TU München
München, , Germany
Friedrich-Ebert-Krankenhaus Neumünster
Neumünster, , Germany
Lukaskrankenhaus Neuss
Neuss, , Germany
Klinikum Nürnberg
Nuremberg, , Germany
Pi.Tri-Studien GmbH Offenburg
Offenburg, , Germany
Klinikum Passau
Passau, , Germany
Schwerpunktpraxis Penzberg
Penzberg, , Germany
Ernst von Bergmann Klinikum Potsdam
Potsdam, , Germany
Studienzentrum Onkologie Ravensburg
Ravensburg, , Germany
Krankenhaus Barmherzige Brüder Regensburg
Regensburg, , Germany
Universitätsklinikum Regensburg
Regensburg, , Germany
Kreiskliniken Reutlingen
Reutlingen, , Germany
Mathias Spital Rheine
Rheine, , Germany
RoMed Klinikum Rosenheim
Rosenheim, , Germany
Universitätsmedizin Rostock
Rostock, , Germany
DIAK Klinikum Schwäbisch Hall
Schwäbisch Hall, , Germany
Marienkrankenhaus Siegen
Siegen, , Germany
Klinikum Stuttgart
Stuttgart, , Germany
Marienhospital Stuttgart
Stuttgart, , Germany
Krankenhaus der Barmherzigen Brüder Trier
Trier, , Germany
Universitätsklinikum Ulm
Ulm, , Germany
Klinikum Wetzlar
Wetzlar, , Germany
Onkologisches Zentrum Wolfsburg-Helmstedt
Wolfsburg, , Germany
Petrus-Krankenhaus Wuppertal
Wuppertal, , Germany
Gemeinschaftspraxis Würzburg
Würzburg, , Germany
Countries
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Central Contacts
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Facility Contacts
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Ludwig Fischer von Weikersthal, Dr.
Role: primary
Daniel Pink, Dr.
Role: primary
Alexander Kiani, Prof. Dr.
Role: primary
Börge Arndt, Dr.
Role: primary
Markus Schuler, Dr.
Role: primary
Annette Dieing, Dr.
Role: primary
Jörg-Christian Rath, Dr.
Role: primary
Anke Reinacher-Schick, Prof. Dr.
Role: primary
Yon-Dschun Ko, Prof. Dr.
Role: primary
Jack Chater, Dr.
Role: primary
Bernhard Sibbing, Dr.
Role: primary
Carl Schimanski, Prof. Dr.
Role: primary
Christian Spoer, Dr.
Role: primary
Gerhard Behre, Prof. Dr.
Role: primary
Lutz Jacobasch, Dr.
Role: primary
Steffen Dörfel
Role: primary
Christoph Roderburg, Prof. Dr.
Role: primary
Christian Müller, Dr.
Role: primary
Stefan Kasper-Virchow, Prof. Dr.
Role: primary
Thorsten Götze, PD Dr.
Role: primary
Silvan Becker, Dr.
Role: primary
Christine Koch, Dr.
Role: primary
Michael Quante, Prof. Dr.
Role: primary
Jochen Wilke, Dr.
Role: primary
Jens Atzpodien, Prof. Dr.
Role: primary
Georg Schließer, Dr.
Role: primary
Yong-Jun Peter Jo, Dr.
Role: primary
Mascha Binder, Prof. Dr.
Role: primary
Marianne Sinn, PD Dr.
Role: primary
Arndt Vogel, Prof. Dr.
Role: primary
Vera Heuer, Dr.
Role: primary
Matthias Glanemann, Prof. Dr.
Role: primary
Udo Lindig, Dr.
Role: primary
Christian Bogner, Dr.
Role: primary
Florian Kaiser, Dr.
Role: primary
Ulrich Hacker, Prof. Dr.
Role: primary
Andrea Heider, Dr.
Role: primary
Christian Constantin, Dr.
Role: primary
Stefan Angermeier, Dr.
Role: primary
Christoph Kahl, Prof. Dr.
Role: primary
Markus Möhler, Prof. Dr.
Role: primary
Christina Balser, Dr.
Role: primary
Jorge Riera, Dr.
Role: primary
Hans-Joachim Tischler, Dr.
Role: primary
Victoria Probst, Dr.
Role: primary
Sylvie Lorenzen, Prof. Dr.
Role: primary
Martin Fuchs, Dr.
Role: primary
Meinolf Karthaus, Prof. Dr.
Role: primary
Christian Lerchenmüller, Dr.
Role: primary
Klaus Wethmar, Dr. Dr.
Role: primary
Siegfried Haas, Dr.
Role: primary
Ulf Reinhart, Dr.
Role: primary
Gabriele Siegler, Dr.
Role: primary
Thomas Südhoff, Prof. Dr.
Role: primary
Michael Sandherr, PD Dr.
Role: primary
Matthias Paland, Dr.
Role: primary
Tobias Dechow, Prof. Dr.
Role: primary
Anke Schlenska-Lange, Dr.
Role: primary
Hans Jürgen Schlitt, Prof. Dr.
Role: primary
Stefan Kubicka, Prof. Dr.
Role: primary
Sebastian Bröckling, Dr.
Role: primary
Gerhard Gerhard Puchtler, Dr.
Role: primary
Ulrich Langenkamp, Dr.
Role: primary
Thomas Geer, Dr.
Role: primary
Elisabeth Mack, Dr.
Role: primary
Wolfram Bohle, Dr.
Role: primary
Iordanis Deligiannis, Dr.
Role: primary
Thomas J. Ettrich, Dr.
Role: primary
Birgitta Killing, Dr.
Role: primary
Matthias Sandmann, Dr.
Role: primary
Björn Schöttker, Dr.
Role: primary
References
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Raschzok N, Stintzing S, Heinemann V, Rauch G, Ricke J, Guckenberger M, Kurreck A, Alig AHS, Stahler A, Bullinger L, Schmelzle M, Schoning W, Lurje G, Krenzien F, Haase O, Rau B, Gebauer B, Sauer IM, Pratschke J, Modest DP. 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. BMC Cancer. 2022 Apr 2;22(1):359. doi: 10.1186/s12885-022-09422-6.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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AIO-KRK-0418
Identifier Type: OTHER
Identifier Source: secondary_id
2020-006144-18
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
FIRE-9 - PORT
Identifier Type: -
Identifier Source: org_study_id
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