NCT07004413

Continuous or Intermittent Cetuximab Plus FOLFIRI as First-line Treatment in RAS/BRAF Wild-type mCRC Patients

Randomized Study to Compare First-line Treatment With Either Continuous or Intermittent Cetuximab Plus FOLFIRI in Patients With RAS/BRAF-wild-type Metastatic Colorectal Cancer (mCRC): AIO-KRK-0524 / FIRE-11

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 267 (estimated)
• Sponsor: Charite University, Berlin, Germany · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to learn if the application of the chemotherapy FOLFIRI and cetuximab works better when given with scheduled breaks or continuously in adults with metastatic colorectal cancer. The main question it aims to answer is, whether worsening of disease after 12 months of treatment is lower when the treatment is given with breaks or given continuously. It will also answer the question whether the quality of life is better and side effects are less if chemotherapy is given with breaks. Additionally, the treatment breaks will be controlled by blood tests and imaging examinations. A novel blood test will be introduced to investigate, whether worsening of the disease might be detected before the imaging, and whether a quicker reaction by re-starting the therapy would help the patients. Participants will: * receive an established chemotherapy mit FOLFIRI and cetuximab * Receive blood tests every 4 weeks and imaging investigations every 12 weeks * fill out questionnaires to report their quality of life

Detailed description

This is a combined multicenter, randomized phase III clinical trial and interventional clinical performance study according to IVDR investigating the superiority of intermittent application of FOLFIRI plus cetuximab followed by a scheduled treatment pause compared to continuous treatment with FOLFIRI plus cetuximab until disease progression or unacceptable toxicity. This study is accompanied by a translational research program. This study protocol is driven by a CTR-conform question and primary endpoint, the PFS from randomization to progression on treatment at 12 months, and supplemented by a separate, complementary, interventional clinical performance study to assess ctDNA as biomarker of early disease progression as a key secondary endpoint. Details regarding the IVD part are specified in the complementary interventional clinical performance study protocol. Treatment is planned until progression, death or unacceptable toxicity. Patients are followed up with regard to survival and if applicable subsequent anti - cancer treatments until death or -after end of study treatment- for at least 3 years after start of treatment, whichever date is earlier.

Conditions

• Colorectal Cancer Metastatic

Interventions

Type	Name	Description
DRUG	FOLFIRI+cetuximab	Cetuximab 500 mg/m², 90 min IV infusion on d1; Irinotecan: 180 mg/m², 90-120 min IV infusion on d1; Folinic acid: 400mg/m², 1-2h IV Infusion on d1; 5-FU: 2400 mg/m², 46 h IV infusion on d1. Cycles are repeated on day 15.
DIAGNOSTIC_TEST	Guardant360 ctDNA assay	Determination of circulating tumor DNA (ctDNA) in the peripheral blood, part 1: retrospective threshold determination to predict radiological disease progression in Arm 2; part 2: prospective validation of the in part 1 identified ctDNA threshold to guide the scheduled treatment breaks and treatment in Arm 2

Timeline

• Start date: 2026-01-01
• Primary completion: 2028-01-01
• Completion: 2031-01-01
• First posted: 2025-06-04
• Last updated: 2025-06-04

Locations

1 site across 1 country: Germany