NCT02934529

Metastatic Colorectal Cancer (RAS-wildtype) After Response to First-line Treatment With FOLFIR Plus Cetuximab

A Randomised Study to Assess the Efficacy of Cetuximab Rechallenge in Patients With Metastatic Colorectal Cancer (RAS Wild-type) Responding to First-line Treatment With FOLFIRI Plus Cetuximab

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 673 (actual)
• Sponsor: Ludwig-Maximilians - University of Munich · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The FIRE-4 study aims to define a treatment concept for patients with RAS wild-type tumours, optimised with regard to overall survival. The first-line treatment will be conducted with FOLFIRI plus cetuximab, which resulted in a significantly prolonged overall survival versus bevacizumab in the FIRE-3 study. Following initial progression (PD1) it is recommended that the treatment be continued with FOLFOX plus bevacizumab, as this concept led to significantly prolonged survival in the E3200 study. Owing to the encouraging results of the Santini study , a cetuximab rechallenge in combination with irinotecan-based chemotherapy is to be performed as part of the third-line treatment in patients who showed a response defined according to RECIST 1.1 during the first-line treatment (tumour diameter \< -30%) or presented with stable tumour disease for at least 6 months (tumour diameter +20 to -30%). The concept of the ideal sequence has not yet been studied to date in a clinical trial.

Detailed description

The study will begin with FPFV: (first study visit of the first patient, signing the declaration of consent to participate in the study): scheduled for the 4th quarter of 2014 Patient recruitment: 36 months Treatment duration per patient: Until the time of progression under the third-line treatment at the latest. Anticipated individual duration of treatment: 24 months (for patients who undergo all three treatment lines -included in part 1), or 6 months in patients who only receive third line treatment (included directly in part 2) Duration of follow-up after the end of treatment: For all patients, until death or for at least 1 year following final termination of any study treatment regardless of the treatment line. In so doing, the follow-up period for patients included in part 1 of the study will be conducted for a maximum of 5 years from the time of randomisation 1; and for patients included in only part 2 of the study (third-line treatment), for a maximum of 3 years from the date of randomisation 2. End of the study: last follow-up visit of the last study patient scheduled for the 4th quarter of 2020

Conditions

• Metastatic Colorectal Cancer

Interventions

Type	Name	Description
DRUG	Irinotecan	Irinotecan 180 mg/m² iv, 30 - 90 min., day 1, q d15
DRUG	Folinic Acid	Folinic acid (racemic) 400 mg/m² iv, 120 min. day 1, q d15
DRUG	5-FU	5-FU 400 mg/m² bolus day 1, q d15
DRUG	5-FU	5-FU 2400 mg/m² iv over 46 h day 1-2, q d15
DRUG	Cetuximab	cetuximab initially 400 mg/m² as a 120 min. infusion (≤ 5mg/min); subsequently 250 mg/m² iv respectively as a 60 min. infusion (≤ 10mg/min) day 1 + 8
DRUG	Bevacizumab	Bevacizumab 7.5 mg/kg BW iv over 30 to 90 minutes: day 1
DRUG	Capecitabine	Capecitabine 1250 mg/m2 2 x day p.o. day 1-14, q d15
DRUG	regorafenib	160 mg per day (day 1-21) (repeated on day 28)
DRUG	Irinotecan 125mg	Irinotecan 125 mg/m² iv, 60 - 90 min. weekly (D1, D8, D15, D22)
DRUG	Cetuximab wkly	Cetuximab initially 400 mg/m² as a 120 min. infusion (≤ 5mg/min); subsequently 250 mg/m² iv respectively as a 60 min. infusion (≤ 10mg/min) weekly (D1, D8, D15, D22, D29, D36)

Timeline

• Start date: 2015-03-01
• Primary completion: 2025-01-30
• Completion: 2025-01-30
• First posted: 2016-10-17
• Last updated: 2025-04-16

Locations

1 site across 1 country: Germany