This prospective, randomized, phase 2 study is conducted to evaluate the efficacy and safety of first line mCapOX plus cetuximab versus mFOLFOX6 plus cetuximab for metastatic left-sided CRC patients with wild-type RAS and BRAF genes.

The patients, who meet the inclusion criteria and have signed the informed consent, will be randomly assigned (1:1 ratio) to receive mCapOX plus cetuximab regimen (arm A) and mFOLFOX6 plus cetuximab regimen (arm B).

Inclusion Criteria:

• Able to provide written informed consent and can understand and comply with the requirements of the study;
• Men and women ≥ 18 years of age;
• Patients with histologically or cytologically confirmed metastatic left-sided colorectal adenocarcinoma with wild-type RAS and BRAF genes;
• Presence of at least one evaluable lesion, as defined in RECIST Version 1.1;
• With an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1;
• No palliative first-line chemotherapy, targeted, immunotherapy, or prior platinum-based adjuvant chemotherapy, relapse more than 12 months from the end of adjuvant chemotherapy;
• According to the imaging findings and surgical assessment of initial unresectable, synchronous metastatic colorectal cancer, no serious complications of the primary tumor (obstruction, perforation, massive hemorrhage that cannot be treated in internal medicine, etc.) ;
• Life expectancy of longer than 3 months ( clinical assessment);
• Requirements for lab indicators neutrophils ≥ 1.5 × 109/L, platelets ≥ 75 × 109/L, hemoglobin ≥ 8 g/dL, total bilirubin ≤ 1.5 × upper limit of normal (UNL); ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 × UNL (≤ 5 × UNL if liver metastases); alkaline phosphatase ≤ 2.5 × UNL (≤ 5 × UNL if liver metastases, ≤ 10 × UNL if bone metastases); LDH < 1500 U/L; creatinine clearance (calculated according to Cockcroft and Gault formula) > 50 mL/min or serum creatinine ≤ 1.5 × UNL;

Exclusion Criteria:

• Patients with mCRC who were initially resectable with R0 resection or radiofrequency or SBRT were excluded.
• Patients diagnosed with MSI-H or dMMR by PCR or immunohistochemistry
• Hypersensitivity to any therapeutic agent.
• Patients who received adjuvant chemotherapy containing oxaliplatin and fluorouracil within 12 months before entering the study;
• Patients who have failed one or more palliative chemotherapy regimens;
• Patients with uncontrolled hepatitis B virus
• Peripheral neuropathy ≥ CTC grade 2;
• Neurological or psychiatric disorders affecting cognitive performance;
• Patients with central nervous system metastasis could not be controlled with radiotherapy;
• Previous enteritis, chronic diarrhea, or recurrent bowel obstruction; uncontrolled bleeding from internal medicine; bowel perforation
• Uncontrolled concomitant diseases within 6 months before the study, including unstable angina, acute myocardial infarction, cerebrovascular accident, etc.;
• Pregnant or lactating patients, or those of childbearing potential who do not take adequate contraceptive measures;
• History of other malignancies, but no disease-free survival longer than 5 years;
• Patients concurrently receiving other anti-tumor treatment or participating in other interventional clinical trials;
• Patients who are unable to comply with this study for psychological, family or social reasons.
• Patients with other serious diseases that the investigator considers not suitable.