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

NCT07176182 | Recruiting Phase 2 DMC

• 1 other identifier: E2025123
• Study Type: interventional
• Target: 236
• Locations: 1 country
• Sites: 1

Brief Summary

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 Patients receiving non-protocol anticancer therapies preoperatively will be withdrawn from the study.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

Conditions

Rectal Cancer Patients; Rectal Cancer Stage II; Rectal Cancer Stage III

Keywords

Neoadjuvant Therapy; mFOLFOX6; Citrus Flavonoid Tablets (Aimailang)

Outcome Measures

Primary Outcomes (1)

• Tumor downstaging rate (to ypTNM stage 0-I)

  The proportion of patients with locally advanced rectal cancer who, after receiving neoadjuvant chemotherapy with mFOLFOX or mFOLFOX plus Citrus flavonoid tablets (Aimailang), were downstaged to ypTNM stage 0-I based on postoperative surgical specimens.

  Perioperative，2 weeks after surgery

Secondary Outcomes (8)

• Three-year disease-free survival

  through study completion, an average of 3 year

• Overall survival

  through study completion, an average of 5 year

• tumor regression grade (TRG)

  Perioperative，2 weeks after surgery

• Rate of Treatment-Related Adverse Events (Grade 3 or Higher)

  through study completion, an average of 1 year

• Complete response (CR) rate

  Perioperative，2 weeks after surgery

Study Arms (2)

mFOLFOX regimen neoadjuvant therapy group

ACTIVE COMPARATOR

Trial Group Description: This trial evaluates the efficacy of combining the mFOLFOX chemotherapy regimen with citrus flavonoid tablets (Aimailang) for neoadjuvant therapy (preoperative). Treatment regimen (4-6 cycles preoperatively): Each 14-day cycle includes: Oxaliplatin: 85 mg/m² intravenous infusion on Day 1, over 180 minutes Calcium folinic acid: 400 mg/m² intravenous infusion on Day 1, over 120 minutes Fluorouracil: 2400 mg/m² continuous intravenous infusion on Day 1, over 46 hours

Drug: mFOLFOX regimen neoadjuvant therapy group

mFOLFOX regimen combined with Citrus Flavone Tablets (Alvenor) neoadjuvant treatment group

EXPERIMENTAL

This trial evaluated a combination regimen of mFOLFOX chemotherapy with citrus flavonoid tablets (Aimailang) for both neoadjuvant (preoperative) and postoperative adjuvant treatment. Treatment Regimen Preoperative (4-6 cycles), each 14-day cycle included. Oxaliplatin: 85 mg/m² intravenous infusion on Day 1, administered over 180 minutes. Calcium folinic acid: 400 mg/m² intravenous infusion on Day 1, over 120 minutes. 5-Fluorouracil: 2400 mg/m², continuous intravenous infusion over 46 hours on Day 1. Citrus Flavonoid Tablets (Aimailang): 500 mg, orally twice daily (Days 1-14), may be used in combination with the chemotherapy regimen or alone (depending on grouping).

Drug: mFOLFOX regimen combined with Citrus Flavone Tablets (Alvenor) neoadjuvant treatment group

Interventions

mFOLFOX regimen neoadjuvant therapy group DRUG

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.

Also known as: 5-Fluorouracil, Oxaliplatin

mFOLFOX regimen neoadjuvant therapy group

mFOLFOX regimen combined with Citrus Flavone Tablets (Alvenor) neoadjuvant treatment group DRUG

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. Citrus flavonoid tablets (Alvenor) : 500 mg orally three times daily (Days 1-14), administered with or without the chemotherapy regimen (depending on group assignment).

Also known as: 5-Fluorouracil, Oxaliplatin, Citrus Flavone Tablets (Alvenor)

mFOLFOX regimen combined with Citrus Flavone Tablets (Alvenor) neoadjuvant treatment group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• Guangdong Provincial People's Hospital: collaborator
• Sixth Affiliated Hospital, Sun Yat-sen University: lead
• Guangzhou First People's Hospital: collaborator
• The First Affiliated Hospital of Guangzhou Medical University: collaborator
• Zhujiang Hospital: collaborator
• Fujian Provincial Hospital: collaborator
• The Third Affiliated Hospital of Guangzhou Medical University: collaborator

Study Sites (1)

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Fluorouracil; Oxaliplatin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Xiaosheng He, M.D./Ph.D

  Sixth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tuo Hu, M.D./Ph.D

CONTACT

+86 13763385541; hutuo3@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This trial evaluated the combination regimen of mFOLFOX chemotherapy with citrus flavonoid tablets (Aimailang) for neoadjuvant (preoperative) and postoperative adjuvant treatment. Treatment Regimen Preoperative (Cycles 4-6), each 14-day cycle included. Oxaliplatin: 85 mg/m² intravenous infusion on Day 1, over 180 minutes. Calcium folinate: 400 mg/m² IV infusion on Day 1, over 120 minutes. Fluorouracil: 2400 mg/m² IV continuous infusion on Day 1, over 46 hours. Citrus Flavonoid Tablets (Aimailang): 500 mg orally twice daily (Days 1-14), may be used in combination with the chemotherapy regimen or as monotherapy (depending on group assignment).

Study Record Dates

• First Submitted: August 27, 2025
• First Posted: September 16, 2025
• Study Start: March 20, 2026
• Primary Completion (Estimated): March 20, 2031
• Study Completion (Estimated): March 20, 2031
• Last Updated: May 26, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)