Pre-Operative Treatment in REseCTable COlon CanceR

NCT06899477 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: PROTECTOR/FIRE-102023-508076-11-00
• Study Type: interventional
• Target: 714
• Locations: 1 country
• Sites: 28

Brief 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 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)).

Conditions

Colo-rectal Cancer; Colon Cancer; Colon Carcinoma

Keywords

colo-rectal cancer; colon; neoadjuvant; upper rectum; pre-operative

Outcome Measures

Primary Outcomes (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.

  LPI + 36 months (96 months total)

Secondary Outcomes (4)

• Overall survival (OS)

  LPI + 60 months (120 months total)

• Tumor regression grades (TRS)

  LPI + 60 months (120 months total)

• (Serious) Adverse Events

  LPI + 60 months (120 months total)

• Quality of life (QoL)

  LPI + 60 months (120 months total)

Study Arms (2)

Arm A: Pre-operative treatment

EXPERIMENTAL

Arm 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

Drug: mFOLFOXIRI; Drug: mFOLFOX-6; Drug: CAPOX

Arm B: Control

NO INTERVENTION

Structured follow-up for at least 60 months after randomization

Interventions

mFOLFOXIRI DRUG

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

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

Arm A: Pre-operative treatment

mFOLFOX-6 DRUG

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.

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

Arm A: Pre-operative treatment

CAPOX DRUG

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

Also known as: Capecitaine, Oxaliplatin

Arm A: Pre-operative treatment

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (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 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.
• 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 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)

You may not qualify if:

• 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.
• 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:

Sponsors & Collaborators

• Dominik Paul Modest: lead
• Frankfurter Institut für Klinische Krebsforschung IKF GmbH: collaborator

Study Sites (28)

Charité Universitätsmedizin Berlin

Berlin, Germany

Location

Ev. Waldkrankenhaus Spandau

Berlin-Spandau, Germany

Location

Klinikum Chemnitz gGmbH

Chemnitz, Germany

Location

St. Elisabeth Krankenhaus GmbH

Cologne, Germany

Location

Städtisches Klinikum Dessau

Dessau, Germany

Location

Gefos Dortmund mbH

Dortmund, Germany

Location

Krankenhaus Nordwest GmbH

Frankfurt, Germany

Location

Hämatologisch Onkologische Praxis Eppendorf (HOPE)

Hamburg, Germany

Location

Evangelisches Krankenhaus Hamm

Hamm, Germany

Location

MediProject GbR

Hanover, Germany

Location

St. Anna Hospital Herne

Herne, Germany

Location

Sana Klinikum Hof

Hof, Germany

Location

Alexianer Krefeld GmbH

Krefeld, Germany

Location

ÜBAG MVZ Dr. Vehling-Kaiser GmbH

Landshut, Germany

Location

Gastroenterologie, Onkologie u. Diabetologie - Theresienkrankenhaus

Mannheim, Germany

Location

GEHO

Münster, Germany

Location

MVZ Media Vita

Münster, Germany

Location

medius Klinik Ostfildern-Ruit

Ostfildern, Germany

Location

Brüderkrankenhaus Sr. Josef

Paderborn, Germany

Location

Kreiskliniken Reutlingen GmbH

Reutlingen, Germany

Location

Mathias Spital - Klinikum Rheine

Rheine, Germany

Location

RoMed Klinikum Rosenheim

Rosenheim, Germany

Location

Leopoldina Krankenhaus

Schweinfurt, Germany

Location

Marien Kliniken - St. Marienkrankenhaus Siegen

Siegen, Germany

Location

MVZ Klinik Dr. Hancken GmbH

Stade, Germany

Location

Lahn-Dill-Kliniken GmbH

Wetzlar, Germany

Location

Remus-Murr-Kliniken gGmbH

Winnenden, Germany

Location

Marien Hospital / MVZ

Witten, Germany

Location

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Leucovorin; Oxaliplatin; Fluorouracil; Irinotecan

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Camptothecin; Alkaloids

Study Officials

• Dominik Modest, Prof. Dr. med.

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dominik Modest, Prof. Dr. med.

CONTACT

+49 30 450; dominik.modest@charite.de

Daniel Müller, Dr.

CONTACT

+49 69 5899 787; mueller.daniel@ikf-khnw.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med.

Model Details: Prospective, randomized, open, multicenter Phase III trial

Study Record Dates

• First Submitted: March 21, 2025
• First Posted: March 28, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): April 1, 2033
• Study Completion (Estimated): April 1, 2035
• Last Updated: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (28)