Clinical Trial of Neoadjuvant mFOLFOX Plus Alvenor for LARC Patients With High YWHAB Expression

This study plans to conduct a prospective, multicenter, open-label, randomized controlled Phase II clinical trial: Endoscopic biopsy specimens from patients with locally advanced rectal cancer will undergo YWHAB immunohistochemical staining to identify those with high YWHAB expression. These patients will be randomly assigned to receive neoadjuvant therapy with either mFOLFOX alone or mFOLFOX combined with citrus flavonoid tablets (Aimailang). Following completion of 4-6 cycles of neoadjuvant chemotherapy, patients will undergo preoperative assessment by the attending physician and tumor resection performed by a specialized colorectal surgical team. This study aims to evaluate the efficacy (tumor downstaging rate, 3-year disease-free survival, overall survival, tumor regression grade [TRG], etc.) and safety (drug-related adverse reactions, etc.) of mFOLFOX combined with citrus flavonoid tablets (Aimailang) neoadjuvant therapy in patients with locally advanced rectal cancer exhibiting high YWHAB expression. Building upon the team's prior basic/translational research, animal studies, and clinical safety data for citrus flavonoid tablets (Aimailang), this study holds promise to enhance treatment outcomes for patients with locally advanced rectal cancer exhibiting high YWHAB expression, thereby benefiting a greater number of patients.

Inclusion criteria

• Histopathologically confirmed rectal adenocarcinoma; all other histologic subtypes are excluded. Presence of hemorrhoids confirmed by colonoscopy or clinical physical examination.
• Radiographically measurable or clinically evaluable rectal tumor lesion; clinical pathologic stage T2N+ or T3-4aAnyN, M0. Clinical staging is determined by physical examination, contrast-enhanced chest and abdominopelvic CT, and pelvic MRI. For patients with MRI contraindications, staging is performed with contrast-enhanced pelvic CT plus transrectal ultrasound. Staging adheres to the 9th AJCC TNM Staging System (Appendix 1).
• Pelvic MRI confirms the tumor is not adherent to the mesorectal fascia (MRF-negative), defined as a tumor-MRF distance ≥ 2 mm (tumor distance < 2 mm is defined as MRF involvement).
• ectal cancer tumor specimens demonstrate high YWHAB expression by immunohistochemistry.
• Age 18-75 years at the time of informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Appendix 3).
• No prior systemic anticancer therapy for rectal cancer, including cytotoxic chemotherapy, immune checkpoint inhibitors, molecular targeted agents, or endocrine therapy.
• Adequate organ function with screening laboratory parameters meeting the following criteria:

• White blood cell count ≥ 3 × 10⁹/L
• Absolute neutrophil count ≥ 1.5 × 10⁹/L
• Platelet count ≥ 75 × 10⁹/L
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN
• Serum creatinine ≤ 1.5 × ULN
• Females of childbearing potential must have a negative serum pregnancy test within 3 days prior to initiation of study treatment and agree to use a highly effective, medically acceptable contraceptive method (e.g., intrauterine device, combined oral contraceptives, barrier methods) throughout the study and for 3 months after the last study drug administration.
• Male patients with partners of childbearing potential must practice effective contraception during the study and for 3 months following the last study drug administration.
• The patient voluntarily provides written informed consent and is willing and able to comply with all scheduled study visits, treatment administration, laboratory assessments, and protocol-specified procedures.