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

Official title

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

Overview

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 Patients receiving non-protocol anticancer therapies preoperatively will be withdrawn from the study.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.

Detailed description

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.

Interventions

• Drug mFOLFOX regimen combined with Citrus Flavone Tablets (Alvenor) neoadjuvant treatment group
  The trial evaluates a regimen combining mFOLFOX chemotherapy with citrus flavonoid tablets (Alvenor) for neoadjuvant therapy (pre-surgery) and postoperative adjuvant therapy. Treatment Protocol Preoperative (4-6 cycles) and Postoperative (6-8 cycles): Each 14-day cycle includes: 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.
• Drug mFOLFOX regimen neoadjuvant therapy group
  The trial evaluates a regimen combining mFOLFOX chemotherapy with citrus flavonoid tablets (Alvenor) for neoadjuvant therapy (pre-surgery) and postoperative adjuvant therapy. Treatment Protocol Preoperative (4-6 cycles) and Postoperative (6-8 cycles): Each 14-day cycle includes: 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.

Primary outcome measures

• Tumor downstaging rate (to ypTNM stage 0-I) [Time frame: Perioperative，2 weeks after surgery]

Secondary outcome measures (8)

• Three-year disease-free survival [Time frame: through study completion, an average of 3 year]
• Overall survival [Time frame: through study completion, an average of 5 year]
• tumor regression grade (TRG) [Time frame: Perioperative，2 weeks after surgery]
• Rate of Treatment-Related Adverse Events (Grade 3 or Higher) [Time frame: through study completion, an average of 1 year]
• Complete response (CR) rate [Time frame: Perioperative，2 weeks after surgery]
• Partial response (PR) rate [Time frame: Perioperative，2 weeks after surgery]
• Stable disease (SD) rate [Time frame: Perioperative，2 weeks after surgery]
• Progressive disease (PD) rate [Time frame: Perioperative，2 weeks after surgery]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Sixth Affiliated Hospital of Sun Yat-sen University — Guangzhou

Identifiers

NCT: NCT07176182 · E2025123

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗