Conversion Therapy of RAS/BRAF Wild-Type Colorectal Cancer Patients With Initially Unresectable Liver Metastases

Colorectal Cancer Clinical Trial

Official title: Conversion Therapy of RAS/BRAF Wild-Type Colorectal Cancer Patients With Initially Unresectable Liver Metastases: mFOLFOXIRI Plus Cetuximab Versus mFOLFOXIRI Plus Bevacizumab

Status Recruiting

Clinical Trial Summary

Evidence suggests that the addition of cetuximab or bevacizumab to doublet regimens could improve response rate and resectability rate of liver metastases and survival in colorectal liver metastases (CRLM). Moreover, it is observed that FOLFOXIRI yields higher response and resection rates compared with doublet regimens. However, which is better in conversion therapy of RAS/BRAF wild-type initially unresectable CRLM, FOLFOXIRI plus cetuximab or bevacizumab, remains unknown.

In this study, RAS/BRAF wild-type colorectal cancer patients with initially unresectable liver-only metastases, as prospectively confirmed by a local multidisciplinary team (MDT) according to predefined criteria, will be randomised between modified FOLFOXIRI (mFOLFOXIRI) plus cetuximab and mFOLFOXIRI plus bevacizumab. Patient imaging will be reviewed for resectability by MDT, consisting of at least one radiologist and three liver surgeons every assessment. MDT review will be performed prior to randomization as well as during treatment, as described in the protocol.

Clinical Trial Description

Patients will be stratified for primary tumor location (right-sided or left sided) and numbers of liver metastases (<5 or ≥5).

Patients with RAS mutated primary tumors will be randomized between mFOLFOXIRI plus cetuximab (cetuximab 500 mg/m^2 in 60 minutes i.v., followed by oxaliplatin 85 mg/m^2 i.v. in 120 minutes, followed by irinotecan 165 mg/m^2 i.v. in 60 minutes, together with leucovorin 400 mg/m^2 i.v. in 120 minutes, followed by continuous infusion of 5-fluorouracil 2400 mg/m^2 in 46 hours, every 2 weeks) or mFOLFOXIRI plus bevacizumab (Bevacizumab 5 mg/kg in 15-30 minutes i.v., followed by oxaliplatin 85 mg/m^2 i.v. in 120 minutes, followed by irinotecan 165 mg/m^2 i.v. in 60 minutes, together with leucovorin 400 mg/m^2 i.v. in 120 minutes, followed by continuous infusion of 5-fluorouracil 2400 mg/m^2 in 46 hours, every 2 weeks).

Patients will be evaluated every 8 weeks by MRI or CT scan for disease status. The assigned systemic treatment should be continued for at least 6 months or earlier in case of resectability, progression of disease, unacceptable toxicity, or patient refusal. If after 6 months MDT concludes that the patient is still not resectable, it is highly unlikely that resectability will be achieved at all. Therefore the chemotherapy regimen may be reconsidered after 6 months of treatment.

In patients who will become resectable and undergo secondary surgery of liver metastases, the total duration of preoperative and postoperative treatment together should be 6 months. However, the postoperative chemotherapy regimen was determined by the investigator. ;

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Liver Metastases
• Liver Neoplasms
• Neoplasm Metastasis
• Neoplasms, Second Primary

• NCT number: NCT04687631
• Study type: Interventional
• Source: Fudan University
• Contact: Jianmin Xu, MD, Ph.D.
• Phone: 86-21-64041990
• Email: xujmin@aliyun.com
• Status: Recruiting
• Phase: Phase 3
• Start date: January 14, 2021
• Completion date: December 31, 2026