mFOLFOXIRI Plus Bevacizumab for Organ Preservation in Locally Advanced Rectal Cancer

Prior treatment

• Concurrent malignant tumors of other organ systems (except malignancies that have been curatively treated with no recurrence for more than 5 years, or carcinoma in situ that can be cured by adequate treatment);
• Thrombotic or embolic events within 12 months prior to enrollment, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, or deep vein thrombosis;
• Within 12 months prior to enrollment, any of the following: myocardial infarction, severe/unstable angina, New York Heart Association (NYHA) class ≥ II cardiac dysfunction, clinically significant supraventricular or ventricular arrhythmia, and symptomatic congestive heart failure;
• Uncontrolled systemic infection or unexplained fever (\>38.5°C) within 2 weeks prior to enrollment;
• Concurrent presence of any of the following other diseases: human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness; poorly controlled diseases including but not limited to non-infectious pneumonitis, diabetes mellitus, hypertension, pulmonary fibrosis, acute pneumonia, aneurysm, and coagulation disorders; or any other disease that, in the investigator's opinion, may affect the assessment of study endpoints;

Other illness

• Bowel obstruction, active gastrointestinal bleeding, or perforation caused by the tumor;
• Tumor complicated by intestinal fistula or pelvic abscess;
• Known or suspected allergy to the study drugs;

Lab values

• Patients with other serious physical or mental illnesses or laboratory abnormalities that may increase the risk of study participation, interfere with study results, or who are considered unsuitable for participation by the investigator.

Other

• Distant metastasis (M1) confirmed by chest/abdominal/pelvic CT, pelvic MRI, or PET-CT;
• Tumors diagnosed as mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) by immunohistochemistry or PCR;
• Pregnant or lactating women;

• Sign the informed consent form and comply with the planned visits, study treatment, laboratory tests, and other trial procedures;
• Age 18-75 years;
• Histologically confirmed rectal adenocarcinoma;
• The lower edge of the rectal tumor is \<10 cm from the anal verge (as assessed by pelvic MRI);
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
• Willing to choose the "organ preservation" strategy according to the study protocol;
• Locally staged as cTNM stage II-III (T3-4 with any N, or any T with N1-2) by contrast-enhanced pelvic MRI;
• No prior antitumor therapy for colorectal cancer, including cytotoxic drugs, radiotherapy, molecular targeted therapy, immune checkpoint inhibitors, etc.;
• Adequate organ function as indicated by the following laboratory values obtained during the screening period: white blood cell count ≥3×10⁹/L, neutrophil count ≥1.5×10⁹/L, platelet count ≥75×10⁹/L, serum total bilirubin ≤1.5× upper limit of normal (ULN), aspartate aminotransferase or alanine aminotransferase ≤2.5× ULN, serum creatinine ≤1.5× ULN.