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Colo-rectal CancerPhase 3NCT06899477

Pre-Operative Treatment in REseCTable COlon CanceR

A Phase 3 study testing mFOLFOXIRI, mFOLFOX-6 and CAPOX in people with Colo-rectal Cancer and Colon Cancer, run by Dominik Paul Modest at 28 sites in Germany.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

This is an open-label, randomized, controlled, multicenter, phase III study with two parallel arms. Patients with advanced colon cancer, including the upper third of the rectum, clinically staged cT3-4 and or cN+ (defined as lymph nodes with short axis of at least 1cm) are randomized in a 2:1 fashion (favoring… Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Colo-rectal Cancer, Colon Cancer, Colon Carcinoma
What is being tested?
mFOLFOXIRI, mFOLFOX-6 and CAPOX
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
714 participants
Where
28 sitesGermany
Study dates
Apr 2025to Apr 2035
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 upper rectum.
  • Confirmed mismatch-repair proficient and/or microsatellite stable tumor. Both Immunohistochemistry and PCR can be used for diagnosis.
  • Intent for curative surgery
  • Predicted T3 or T4 stage and or nodal positivity (N+) in a computed tomography and/or magnetic resonance imaging scan of the abdomen/pelvis as assessed by the local study team.
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  • T3-4 defined as invasion of surrounding tissue structures or organs
  • N+ defined as regional lymph node(s) without fat hilus and short axis diameter of ≥1 cm
  • Absence of clear distant metastases assessed by the investigator based on respective routine evaluations within 6 weeks prior to inclusion into the trial (preferred: computed tomography of thorax and abdomen. Alternatively magnetic resonance images, sonography and x-rays might be used for assessment).
  • Absence of significant active wound healing including severe chronic non-healing wounds, ulcerous lesions or untreated bone fracture
  • 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 (1,500/µL)
  • Hemoglobin ≥ 80 g/L (8 g/dL) with or without transfusion
  • Platelet count ≥ 100 x109/L (100,000/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:
  • Prior treatment with 5-FU or capecitabine without unusal toxicity or
  • If tested, normal DPD deficiency test according to the standard of the study site or
  • If tested, in patients with DPD deficiency test with a CPIC activity score of 1.0-1.5 fluoropyrimidine dosage should be reduced by 50%
  • For women of childbearing potential (WOCBP): negative pregnancy test within 7 days before treatment initiation 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 6 months after the last dose of 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.
  • With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for 6 months after the last dose of study medication to avoid exposing the embryo.

Who cannot join

  • Ileus or directly imminent ileus as assessed by the local study team. Patients with treated and resolved ileus are allowed into the trial.
  • Previous chemotherapy for colorectal cancer of any stage
  • 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.
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  • Ongoing toxicities > grade 2 NCI CTCAE, in particular peripheral neuropathy.
  • Active uncontrolled infection by investigator's perspective.
  • Known hypersensitivity to 5-FU, folinic acid, capecitabine, irinotecan or oxaliplatin 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)).
  • Simultaneous application of St. John's Wort preparations.
  • Pernicious or other megaloblastic anemia caused by vitamin B12 deficiency.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 21 days prior to randomization that may interfere with systemic therapy as judged by the investigator.
  • 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, including but not limited to:
  • Simultaneous application of live vaccines during treatment with irinotecan and for at least 6 months after the last dose.
  • 5-FU must not be given in combination with brivudin, sorivudin and analogues to patients homozygous for DPD and patients known with completely missing DPD activity.
  • Severe diarrhoea.
  • Medical history of malignant disease other than colorectal cancer 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
  • Known alcohol or drug abuse.
  • Pregnant or breastfeeding females.
  • 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.
  • Patients depended on Sponsor, investigator or study site.
  • Patient committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
  • Limited legal capacity

Trial locations and contacts

28 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Dominik Modest, Prof. Dr. med. contact

+49 30 450 ext. 553222

dominik.modest@charite.de

Daniel Müller, Dr. contact

+49 69 5899 787 ext. 22

mueller.daniel@ikf-khnw.de

28 sites in 1 country

Germany28 sites

  • Charité Universitätsmedizin Berlin

    Berlin

    Dominik Modest, Prof. Dr. med.

  • Ev. Waldkrankenhaus Spandau

    Berlin-Spandau

  • Klinikum Chemnitz gGmbH

    Chemnitz

  • St. Elisabeth Krankenhaus GmbH

    Cologne

  • Städtisches Klinikum Dessau

    Dessau

  • Gefos Dortmund mbH

    Dortmund

  • Krankenhaus Nordwest GmbH

    Frankfurt

  • Hämatologisch Onkologische Praxis Eppendorf (HOPE)

    Hamburg

  • Evangelisches Krankenhaus Hamm

    Hamm

  • MediProject GbR

    Hanover

    Michael Gärtner, Dr.

  • St. Anna Hospital Herne

    Herne

  • Sana Klinikum Hof

    Hof

  • Alexianer Krefeld GmbH

    Krefeld

  • ÜBAG MVZ Dr. Vehling-Kaiser GmbH

    Landshut

  • Gastroenterologie, Onkologie u. Diabetologie - Theresienkrankenhaus

    Mannheim

  • GEHO

    Münster

  • MVZ Media Vita

    Münster

  • medius Klinik Ostfildern-Ruit

    Ostfildern

  • Brüderkrankenhaus Sr. Josef

    Paderborn

  • Kreiskliniken Reutlingen GmbH

    Reutlingen

  • Mathias Spital - Klinikum Rheine

    Rheine

  • RoMed Klinikum Rosenheim

    Rosenheim

  • Leopoldina Krankenhaus

    Schweinfurt

  • Marien Kliniken - St. Marienkrankenhaus Siegen

    Siegen

  • MVZ Klinik Dr. Hancken GmbH

    Stade

  • Lahn-Dill-Kliniken GmbH

    Wetzlar

  • Remus-Murr-Kliniken gGmbH

    Winnenden

  • Marien Hospital / MVZ

    Witten

Other trials in Germany

About this study

Official title: Pre-Operative Treatment in REseCTable COlon CanceR (PROTECTOR/FIRE-10; AIO-KRK-0620; IAG-VO-0323) Prospective, Randomized, Open, Multicenter Phase III Trial to Investigate the Efficacy Preoperative Systemic Therapy in Advanced Colon Cancer

This is an open-label, randomized, controlled, multicenter, phase III study with two parallel arms. Patients with advanced colon cancer, including the upper third of the rectum, clinically staged cT3-4 and or cN+ (defined as lymph nodes with short axis of at least 1cm) are randomized in a 2:1 fashion (favoring preoperative therapy= Arm A) to investigate the efficacy, patient reported quality of life and safety of preoperative mFOLFOXIRI or mFOLFOX-6 or CAPOX followed by surgery versus the standard of care algorithm (surgery followed by stage-guided adjuvant therapy as recommended by the local multidisciplinary tumor board (Arm B)).

Read the detailed description

The trial will consist of a clinical and translational part. After completion of the treatment algorithm in both arms of the trial, follow-up as scheduled by current guidelines is recommended. Additionally, assessment of quality of life and blood sampling (tumor markers, circulating tumor DNA and potential innovative markers) will be performed for up to 5 years on a three-months basis. During the active part of the study, a radiologic re-assessment prior to surgery will be recommended for all trial subjects of arm A. Tumor biopsies and resected tumor specimens will be collected at screening (baseline sample) and in the course of treatment. Additionally, in case of disease relapse a tumor re-biopsy will be collected as far as considered feasible and safe for the patient by the investigator.

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).

Patients in Arm A will receive a preoperative study drug intervention (mFOLFOXIRI or mFOLFOX-6 or CAPOX) for up to 3 months (6 cycles biweekly or 4 cycles triweekly) after randomization with clinical and safety assessments as specified in (Table 1).

Allocation to study treatment FOLFOX/FOLFOXIRI or CAPOX for patients in Arm A is stratified and done by investigator's choice. Beyond clinical or radiological factors, the decision may consider but is not limited to factors such as age, performance status, and patients' perspectives. Since obligatory criteria cannot be made, treatment allocation will not be regulated by the protocol, but stratification will avoid that treatment allocation promotes bias.

Being tested
mFOLFOXIRI, mFOLFOX-6, CAPOX
Keywords
colo-rectal cancer, colon, neoadjuvant, upper rectum, pre-operative
Medical subject headings
Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • mFOLFOXIRIDrug

    Also called Folinic acid, Oxaliplatin, 5-FU, Irinotecan

    Up to 6 cycles, every 2 weeks, mFOLFOXIRI: Oxaliplatin 85 mg/m2 2 h day 1, Irinotecan 150 mg/m2 60-90 min day 1, Folinic acid 400 mg/m2 ~1 h day 1, followed by 5-FU 2400 mg/m2 46 h

  • mFOLFOX-6Drug

    Also called Folinic acid, Oxaliplatin, 5-fluorouracil (FU)

    Up to 6 cycles, every 2 weeks, mFOLFOX-6: Oxaliplatin 85 mg/m2 2 h day 1, Folinic acid 400 mg/m2 ~1 h day 1, (optional: 5-FU 400 mg/m2 bolus), followed by 5-FU 2400 mg/m2 46 h.

  • CAPOXDrug

    Also called Capecitaine, Oxaliplatin

    Up to 4 cycles, every 3 weeks, CAPOX: Oxaliplatin 130 mg/m2 3 h day 1, Capecitabine 1000 mg/m2 ORALLY taken twice daily d1-d14

Study groups in NCT06899477
Study groupRoleWhat they receive
Arm A: Pre-operative treatmentExperimentalArm A: choice of one of the offered pre-operative regimens: 1. Up to 6 cycles, every 2 weeks, mFOLFOXIRI 2. Up to 6 cycles, every 2 weeks, mFOLFOX-6 3. Up to 4 cycles, every 3 weeks, CAPOX followed by structured Follow-up for up to 60months after randomization
Receives: Drug: mFOLFOXIRI; Drug: mFOLFOX-6; Drug: CAPOX
Arm B: ControlNo interventionStructured follow-up for at least 60 months after randomization

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease-free survival (DFS)

    Disease-free survival (DFS) - defined as no surgery, no resection, incomplete resection, disease recurrence (new metastases or local relapse) and death from any cause from the time of randomization. In case of no surgery ,no resection, or incomplete resection (defined as R2 resection = macroscopic tumor rest), the timepoint of the respective event will be set to two weeks after randomization to avoid time-bias in favor of the experimental/neoadjuvant therapy arm.

    Measured: LPI + 36 months (96 months total)

Secondary outcomes (4)

  1. Overall survival (OS)

    time from randomization to the date of death of any cause

    Measured: LPI + 60 months (120 months total)

  2. Tumor regression grades (TRS)

    according to Dworak's score

    Measured: LPI + 60 months (120 months total)

  3. (Serious) Adverse Events

    Type, incidence, severity, and causal relationship to active chemotherapy of non-serious adverse events and serious adverse events (severity evaluated according to CTCAE version 5.0), rate of surgery complication scores (Clavien Dindo)

    Measured: LPI + 60 months (120 months total)

  4. Quality of life (QoL)

    assessed with the QoL questionnaire EQ-5D-5L

    Measured: LPI + 60 months (120 months total)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2025
  2. Study startApr 2025 (estimated)
  3. Primary completionApr 2033 (estimated)
  4. Study completionApr 2035 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Prospective, randomized, open, multicenter Phase III trial
Masking
None (open label)
Enrolment
714 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06899477
Sponsor's protocol ID
PROTECTOR/FIRE-10
Other IDs
2023-508076-11-00, 2023
Status last verified
Mar 2025
First submitted
21 Mar 2025
Last updated
28 Mar 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Siegel R, Dittrich L, Plewe J, Denecke T, Leonhardi J, Tannapfel A, Reinacher-Schick A, Raschzok N, Sauer IM, Lauscher J, Lorenzen S, Gotze T, Jelas I, Stahler A, Kurreck A, Ballhausen A, Ostendorf BN, Haase O, Pratschke J, Stintzing S, Modest DP. 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. BMC Cancer. 2026 Mar 20;26(1):454. doi: 10.1186/s12885-026-15682-3.

    PubMed 41857556

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing mFOLFOXIRI, mFOLFOX-6 and CAPOX in people with Colo-rectal Cancer and Colon Cancer, run by Dominik Paul Modest at 28 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 28 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Dominik Modest, Prof. Dr. med. (+49 30 450 ext. 553222, dominik.modest@charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease-free survival (DFS) (time frame: LPI + 36 months (96 months total)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06899477, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2025.

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