FOLFOX8 Versus mFOLFOX6 With Bevacizumab or Cetuximab for First-Line Unresectable Metastatic Colorectal Cancer (Phase II)

This is a prospective, multicenter, randomized controlled, phase II study. It is expected to enroll 229 patients and aims to evaluate the efficacy and safety of FOLFOX8 versus mFOLFOX6 combined with bevacizumab or cetuximab as first-line treatment for unresectable metastatic colorectal cancer. The primary objective is to assess progression-free survival (PFS) of the patients. Secondary objectives include assessment of objective response rate (ORR), overall survival (OS), safety, and other outcomes.

Inclusion Criteria: 1. Age ≥ 18 years, male or female. 2. ECOG performance status 0-2. 3. Histologically or cytologically confirmed unresectable metastatic colorectal cancer with no prior treatment for unresectable or metastatic disease. 4. Adequate organ function: Hb ≥ 70 g/L; WBC ≥ 3.0×10⁹/L; NEUT ≥ 1.5×10⁹/L; PLT ≥ 75×10⁹/L; AST and ALT ≤ 3× ULN; sCr ≤ 2× ULN; TBIL ≤ 2× ULN. 5. Expected survival \> 3 months. Exclusion Criteria: 1. Known allergy to the study drug(s) and/or their excipients. 2. Contraindications to chemotherapy. 3. Patients with MSI-H or dMMR colorectal cancer. 4. Patients with BRAF mutation. 5. Pregnant or breastfeeding women. 6. History of any second malignancy within 2 years prior to randomization, except for cured localized tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, cervical carcinoma in situ, or breast carcinoma in situ, which are allowed for enrollment. 7. Patients with systemic medical or psychiatric disorders that make them unsuitable for chemotherapy. 8. Patients deemed unsuitable for enrollment in this study by the investigator's judgment. 9. Participation in another clinical trial of an investigational drug within 4 weeks prior to randomization.