Neoadjuvant Therapy （NALIRIFOX） for Locally Advanced Colon and Upper Rectal Cancer

Prior treatment

• Patients who are known to be allergic or intolerant to the investigational drug or its excipients in this study;
• Any clinical indicators showing contraindications for chemotherapy and surgery;
• Patients using strong inhibitors or inducers of CYP3A4, CYP2C8, and UGT1A1, etc.;
• Patients who have participated in other clinical trials within 4 weeks prior to enrollment;

Other illness

• Patients who have had other malignant tumors within the past 5 years (except for cured and non-recurring carcinoma in situ, basal cell carcinoma of the skin, etc.);
• Patients with active, uncontrolled bacterial, viral, or fungal infections requiring systemic treatment, defined as persistent signs/symptoms related to infection that do not improve despite appropriate antibiotics, antiviral therapy, and/or other treatments;

Lab values

• Patients with uncontrolled systemic diseases, including unstable angina, myocardial infarction, congestive heart failure, severe unstable ventricular arrhythmias, history of severe pericardial disease, and other cardiovascular diseases; uncontrolled hypertension (defined as a systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg despite standardized antihypertensive treatment), or a history of hypertensive crisis or hypertensive encephalopathy; uncontrolled diabetes (fasting blood glucose ≥10 mmol/L);

Other

• Pregnant or breastfeeding women, and women of childbearing potential who refuse to use appropriate contraception during the trial;
• Patients deemed unsuitable for participation in this study by the investigator.

• Aged 18-75 years, both male and female are eligible;
• ECOG score of 0-1;
• Biopsy-confirmed pathological diagnosis of advanced-stage colon cancer or upper rectal cancer;
• Clinical staging of T3N+ or T4Nany with initially resectable disease;
• Routine chest and abdominal CT scans show no distant metastases;
• Bone marrow function: neutrophils (ANC) ≥1.5×10\^9/L, platelets (PLT) ≥100×10\^9/L, hemoglobin (Hb) ≥70g/L;
• Liver function: ALT, AST ≤2.5×ULN (upper limit of normal); total bilirubin ≤1.5×ULN; serum albumin ≥3 g/dL;
• Kidney function: serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥60 ml/min (calculated using Cockcroft-Gault formula);
• For female patients and those with reproductive potential, a negative pregnancy test must be conducted ≤72 hours prior to starting the study treatment, and they must agree to avoid pregnancy during the study treatment and for 6 months after the study treatment. For male patients with reproductive potential partners, they must agree to use adequate, medically approved contraception during the last study treatment and for 90 days afterward;
• Must be willing to undergo the neoadjuvant chemotherapy regimen in this study and sign an informed consent form.