mFOLFOX6 Combined With Citrus Flavonoid Tablets (Aimailang) as Neoadjuvant Therapy for Locally Advanced Rectal Cancer With High YWHAB Expression: A Prospective, Multi-center, Open-Label, Randomized Controlled Phase II Clinical Trial
This study is a prospective, multicenter, open-label, randomized controlled Phase II clinical trial enrolling patients with locally advanced rectal cancer who tested positive for YWHAB (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase-activating protein β) prior to surgery. The trial aims to evaluate the efficacy of combining the mFOLFOX chemotherapy regimen with citrus flavonoid tablets (Aimilang) for neoadjuvant (preoperative) treatment. Treatment Regimen 4-6 cycles preoperatively, with each cycle lasting 14 days. Translated with DeepL.com (free version) Oxaliplatin: 85 mg/m² via 180-minute intravenous infusion on Day 1. Leucovorin: 400 mg/m² via 120-minute intravenous infusion on Day 1. 5-Fluorouracil: 2400 mg/m² via continuous intravenous infusion over 46 hours. Citrus flavonoid tablets (Aimailang) : 500 mg orally twice times daily (Days 1-14), administered with or without the chemotherapy regimen (depending on group assignment). Key Trial Design Features Dose Adjustments: Permitted during the trial based on patient tolerance. Discontinuation Criteria: Patients with disease progression during neoadjuvant therapy will cease study treatment and proceed to surgery or alternative therapies per local guidelines. Surgery may be initiated early if patients cannot tolerate the planned 6 cycles of neoadjuvant therapy. Patients receiving non-protocol anticancer therapies preoperatively will be withdrawn from the study. Postoperative Management: Post-treatment plans (e.g., continuation of mFOLFOX + Aimailang) are determined by the investigator. Control Group Restriction: Patients in the control arm are not permitted to self-administer citrus flavonoid tablets (Aimailang) during the trial. Any requirement for this medication must be discussed with the treating physician, who will decide on alternative therapies or trial withdrawal.
• 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.