NCT07012954

ctDNA-Guided Cetuximab or Bevacizumab Plus Trifluridine/Tipiracil in RAS/BRAF Wild-Type mCRC

ctDNA-Guided Rechallenge With Cetuximab Plus Trifluridine/Tipiracil Versus Bevacizumab Plus Trifluridine/Tipiracil for RAS/BRAF Wild-Type Refractory Metastatic Colorectal Cancer: A Randomized Clinical Trial

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 64 (estimated)
• Sponsor: Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The objective of this randomized controlled clinical trial is to evaluate the efficacy of ctDNA-guided rechallenge with cetuximab plus trifluridine/tipiracil compared with bevacizumab plus trifluridine/tipiracil in patients with treatment-refractory, RAS/BRAF wild-type metastatic colorectal cancer.

Detailed description

Colorectal cancer (CRC) remains a major public health challenge in China, where its incidence and mortality continue to rise. Although surgical resection is the cornerstone of curative treatment, metastatic disease develops in 30-40% of patients. Anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies such as cetuximab and panitumumab are pivotal therapeutic agents for patients with RAS wild-type metastatic colorectal cancer (mCRC), exerting antitumor effects through inhibition of the EGFR pathway and activation of antibody-dependent cell-mediated cytotoxicity. Recent evidence from phase II trials and retrospective analyses has suggested that rechallenge with anti-EGFR monoclonal antibodies in later-line settings may confer clinical benefit in selected patients who previously responded to first-line anti-EGFR-based therapy. Studies such as CRICKET and CHRONOS have highlighted the feasibility of this approach, with emerging data supporting the utility of circulating tumor DNA (ctDNA) to guide patient selection based on RAS, BRAF, and EGFR extracellular domain mutation status. Notably, the VELO study demonstrated improved progression-free survival (PFS) with third line panitumumab plus trifluridine/tipiracil compared to trifluridine/tipiracil alone, particularly in patients with ctDNA-confirmed RAS/BRAF wild-type status. Similarly, the ongoing PARERE and recently reported CITRIC studies have further emphasized the value of molecular stratification using liquid biopsy to refine anti-EGFR rechallenge strategies and optimize treatment sequencing. The current study builds upon these findings and aims to evaluate and compare the efficacy and safety of cetuximab plus trifluridine/tipiracil versus bevacizumab plus trifluridine/tipiracil as later-line treatments in Chinese patients with RAS/BRAF wild-type mCRC, with treatment selection informed by ctDNA profiling. By integrating real-world clinical data and contemporary molecular diagnostics, this study seeks to assess the potential benefit of cetuximab-based rechallenge therapy in a population with limited therapeutic options and to contribute further evidence supporting the implementation of personalized, biomarker-guided strategies in later-line mCRC management.

Conditions

• Colorectal Cancer Metastatic

Interventions

Type	Name	Description
DRUG	Cetuximab (Erbitux, C225)	cetuximab 500 mg/m² repeated every two weeks.
DRUG	trifluridine/tipiracil	Trifluridine/tipiracil 35 mg/m² (orally for 5 days, followed by 9 days off)
DRUG	Bevacizumab ( Avastin)	bevacizumab 5 mg/kg

Timeline

• Start date: 2025-06-01
• Primary completion: 2027-12-31
• Completion: 2030-12-31
• First posted: 2025-06-10
• Last updated: 2025-06-24

Locations

1 site across 1 country: China