NCT05008809

Brief Summary

This is an open-label, randomized, controlled, multicenter, phase III study with two parallel arms. Patients with metastatic colorectal cancer after definite interventional therapy of all lesions are randomized in a 2:1 fashion (favoring active therapy) to investigate the efficacy, patient reported quality of life and safety of mFOLFOXIRI/mFOLFOX-6 as additive treatment (Arm A) versus active follow-up/surveillance (Arm B).

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
507

participants targeted

Target at P50-P75 for phase_3 colorectal-cancer

Timeline
53mo left

Started Dec 2021

Longer than P75 for phase_3 colorectal-cancer

Geographic Reach
1 country

79 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress51%
Dec 2021Nov 2030

First Submitted

Initial submission to the registry

August 6, 2021

Completed
11 days until next milestone

First Posted

Study publicly available on registry

August 17, 2021

Completed
4 months until next milestone

Study Start

First participant enrolled

December 6, 2021

Completed
5.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2027

Expected
3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2030

Last Updated

December 12, 2025

Status Verified

December 1, 2025

Enrollment Period

5.9 years

First QC Date

August 6, 2021

Last Update Submit

December 5, 2025

Conditions

Keywords

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

  • Progression-free survival (PFS) time

    time from randomization to death or evidence of disease relapse/progression (whatever occurs first)

    24 months

Secondary Outcomes (4)

  • Overall survival (OS)

    at least 5 years after randomization

  • Control ol lesions

    up to 5 years after randomization

  • (Serious) Adverse Events

    up to 2 years after randomization

  • Quality of life (QoL)

    up to 5 years after randomization

Study Arms (2)

Treatment

EXPERIMENTAL

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

Drug: mFOLFOX6Drug: mFOLFOXIRIDrug: FOLFIRIDrug: CAPOX

Control

NO INTERVENTION

Structured Follow-up for up to five years after randomization

Interventions

CAPOXDRUG

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.

Also known as: Capecitaine, Oxaliplatin
Treatment

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.

Also known as: Folinic acid, Oxaliplatin, 5-fluorouracil (FU)
Treatment

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.

Also known as: Folinic acid, Oxaliplatin, 5-FU, Irinotecan
Treatment

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.

Also known as: Folinic acid, 5-FU
Treatment

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patient's signed informed consent.
  • Patient's age ≥18 years at the time of signing the informed consent.
  • Histologically confirmed adenocarcinoma of the colon or rectum.
  • 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.
  • 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.
  • ECOG performance status 0-2.
  • 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
  • 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.
  • Proficient fluorouracil metabolism as defined:
  • +6 more criteria

You may not qualify if:

  • Treatment of metastases greater than 3 cm with radio-frequency/microwave ablation within 24 months prior to study entry if applicable.
  • Treatment of metastases greater than 5 cm with radiation (stereotactic/ brachytherapy) within 24 months prior to study entry if applicable.
  • 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
  • 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).
  • New York Heart Association Class III or greater heart failure by clinical judgement.
  • Myocardial infarction within 6 months prior to randomization; percutaneous transluminal coronary angioplasty (PTCA) with or without stenting within 6 months prior to randomization.
  • Unstable angina pectoris.
  • Unstable cardiac arrhythmia \> grade 2 NCI CTCAE despite anti-arrhythmic therapy.
  • Ongoing toxicities \> grade 2 NCI CTCAE
  • Active uncontrolled infection by investigator's perspective.
  • Severe chronic non-healing wounds, ulcerous lesions or untreated bone fracture.
  • 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.
  • Recent or concomitant treatment with brivudine.
  • Peripheral sensitive neuropathy with functional impairment (\> grade 1 acc. to CTCAE version 5.0 (see appendix 2)).
  • Inflammatory bowel disease and/or bowel obstruction.
  • +16 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (79)

Klinikum St. Marien Amberg

Amberg, Germany

RECRUITING

Helios Klinikum Bad Saarow

Bad Saarow, Germany

RECRUITING

Klinikum Bayreuth

Bayreuth, Germany

RECRUITING

Charité Universitätsmedizin Berlin

Berlin, 13353, Germany

RECRUITING

Helios Klinikum Emil von Behring

Berlin, Germany

RECRUITING

MVZ Onkologischer Schwerpunkt am Oskar-Helene-Heim

Berlin, Germany

RECRUITING

Vivantes Klinikum am Urban Berlin

Berlin, Germany

RECRUITING

Vivantes Klinikum Spandau Berlin

Berlin, Germany

RECRUITING

St. Josef-Hospital Bochum

Bochum, Germany

RECRUITING

Johanniterkrankenhaus Bonn

Bonn, Germany

RECRUITING

Diakonie-Krankenhaus Bremen

Bremen, Germany

WITHDRAWN

Klinikum Chemnitz

Chemnitz, Germany

RECRUITING

Kliniken der Satdt Köln

Cologne, Germany

RECRUITING

Klinikum Darmstadt

Darmstadt, Germany

RECRUITING

DONAUISAR Klinikum Deggendorf

Deggendorf, Germany

RECRUITING

Städtisches Klinikum Dessau

Dessau, Germany

RECRUITING

Onkologische-Gemeinschaftspraxis Dresden

Dresden, Germany

RECRUITING

Onkozentrum Dresden

Dresden, Germany

RECRUITING

Universitätsklinikum Düsseldorf

Düsseldorf, Germany

RECRUITING

Kliniken Essen-Mitte

Essen, Germany

RECRUITING

Universitätsklinikum Essen

Essen, Germany

RECRUITING

KHNW Frankfurt

Frankfurt, Germany

RECRUITING

Markus-Krankenhaus Frankfurt

Frankfurt, Germany

RECRUITING

Universitätsklinikum Frankfurt

Frankfurt, Germany

RECRUITING

Universitätsklinikum Freiburg

Freiburg im Breisgau, Germany

RECRUITING

Gemeinschaftspraxis internistische Onkologie Fürth

Fürth, Germany

RECRUITING

Niels-Stensen Kliniken Georgsmarienhütte

Georgsmarienhütte, Germany

RECRUITING

Praxis Hämatologie Onkologie Gießen

Giessen, Germany

RECRUITING

Universitätsmedizin Göttingen

Göttingen, Germany

RECRUITING

Universitätsklinikum Halle

Halle, Germany

RECRUITING

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, Germany

RECRUITING

St. Anna Hospital Herne

Herne, Germany

RECRUITING

Universitätsklinikum des Saarlandes

Homburg, Germany

RECRUITING

Klinikum Ingolstadt GmbH

Ingolstadt, Germany

WITHDRAWN

Universitätsklinikum Jena

Jena, Germany

RECRUITING

Klinikum Landshut

Landshut, Germany

RECRUITING

VK&K Studien Landshut

Landshut, Germany

RECRUITING

Studienzentrum UnterEms Leer

Leer, Germany

ACTIVE NOT RECRUITING

Universitätsklinikum Leipzig

Leipzig, Germany

RECRUITING

Klinikum Leverkusen

Leverkusen, Germany

RECRUITING

Klinikum Lippe

Lippe, Germany

RECRUITING

Klinikum Ludwigsburg

Ludwigsburg, Germany

RECRUITING

Klinikum Magdeburg

Magdeburg, Germany

RECRUITING

Universitätsmedizin Mainz

Mainz, Germany

RECRUITING

OnkoNet Marburg GmbH

Marburg, Germany

RECRUITING

Philipps-Universität Marburg

Marburg, Germany

RECRUITING

Johannes Wesling Klinikum Minden

Minden, Germany

RECRUITING

Kliniken Maria Hilf Mönchengladbach

Mönchengladbach, Germany

WITHDRAWN

Klinikum der Universität München

München, Germany

RECRUITING

Klinikum rechts der Isar TU München

München, Germany

RECRUITING

München Klinik Bogenhausen

München, Germany

RECRUITING

München Klinik Neuperlach

München, Germany

RECRUITING

Gemeinschaftspraxis Münster

Münster, Germany

RECRUITING

Universitätsklinikum Münster

Münster, Germany

RECRUITING

Friedrich-Ebert-Krankenhaus Neumünster

Neumünster, Germany

RECRUITING

Lukaskrankenhaus Neuss

Neuss, Germany

RECRUITING

Klinikum Nürnberg

Nuremberg, Germany

RECRUITING

Pi.Tri-Studien GmbH Offenburg

Offenburg, Germany

WITHDRAWN

Klinikum Passau

Passau, Germany

RECRUITING

Schwerpunktpraxis Penzberg

Penzberg, Germany

RECRUITING

Ernst von Bergmann Klinikum Potsdam

Potsdam, Germany

RECRUITING

Studienzentrum Onkologie Ravensburg

Ravensburg, Germany

RECRUITING

Krankenhaus Barmherzige Brüder Regensburg

Regensburg, Germany

RECRUITING

Universitätsklinikum Regensburg

Regensburg, Germany

RECRUITING

Kreiskliniken Reutlingen

Reutlingen, Germany

RECRUITING

Mathias Spital Rheine

Rheine, Germany

RECRUITING

RoMed Klinikum Rosenheim

Rosenheim, Germany

RECRUITING

Universitätsmedizin Rostock

Rostock, Germany

RECRUITING

DIAK Klinikum Schwäbisch Hall

Schwäbisch Hall, Germany

RECRUITING

Marienkrankenhaus Siegen

Siegen, Germany

RECRUITING

Klinikum Stuttgart

Stuttgart, Germany

RECRUITING

Marienhospital Stuttgart

Stuttgart, Germany

WITHDRAWN

Krankenhaus der Barmherzigen Brüder Trier

Trier, Germany

RECRUITING

Universitätsklinikum Ulm

Ulm, Germany

RECRUITING

Klinikum Wetzlar

Wetzlar, Germany

RECRUITING

Onkologisches Zentrum Wolfsburg-Helmstedt

Wolfsburg, Germany

WITHDRAWN

Petrus-Krankenhaus Wuppertal

Wuppertal, Germany

RECRUITING

Gemeinschaftspraxis Würzburg

Würzburg, Germany

RECRUITING

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

LeucovorinOxaliplatinFluorouracilIrinotecanIFL protocol

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

FormyltetrahydrofolatesTetrahydrofolatesFolic AcidPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsCoenzymesEnzymes and CoenzymesCoordination ComplexesOrganic ChemicalsUracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingCamptothecinAlkaloids

Study Officials

  • Dominik Modest, Prof. Dr.

    Charite University, Berlin, Germany

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Dominik Modest, Prof. Dr.

CONTACT

Daniel Müller, Dr.

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: open-label, randomized, controlled, multicenter, phase III study with two parallel arms
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Prof. Dr. med.

Study Record Dates

First Submitted

August 6, 2021

First Posted

August 17, 2021

Study Start

December 6, 2021

Primary Completion (Estimated)

November 1, 2027

Study Completion (Estimated)

November 1, 2030

Last Updated

December 12, 2025

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will not share

Locations