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

NCT07176182 | Not Yet 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, open-label, two-arm, phase II clinical trial involving patients preoperatively diagnosed with YWHAB (Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta)-high locally advanced rectal cancer. The trial evaluates a regimen combining mFOLFOX chemotherapy with citrus flavonoid tablets (Aimailang) 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 (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 Patients receiving non-protocol anticancer therapies preoperatively will be withdrawn from the study.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 (Alvenor): 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 histological types are excluded. The patients have concurrent hemorrhoids documented by colonoscopy report or clinical physical examination.
• Clinical Pathological Stage: Tumor staged as T3-4 or N+, M0 (according to the AJCC （American Joint Committee on Cancer）TNM （Tumor-Node-Metastasis) Staging System, 9th Edition; see Appendix 1).
• Biomarker Status: Immunohistochemical staining of the tissue specimen demonstrates high expression of YWHAB in rectal cancer.
• Age: 18 to 75 years old, inclusive, at the time of signing the Informed Consent Form (ICF).
• Performance Status: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (see Appendix 3).
• Prior Therapy: No prior systemic anti-tumor therapy for rectal cancer, including cytotoxic chemotherapy, immune checkpoint inhibitor therapy, molecular targeted therapy, endocrine therapy, etc.
• Adequate Organ Function: Based on laboratory values obtained during the screening period:White Blood Cell (WBC) count ≥ 3.0 × 10⁹/L, absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L, platelet count ≥ 75 × 10⁹/L, serum Total Bilirubin ≤ 1.5 × Upper Normal Limit (UNL), aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) ≤ 2.5 × UNL, serum Creatinine ≤ 1.5 × UNL.
• Contraception (Females of Childbearing Potential - FCBP): FCBP must have a negative serum pregnancy test within 3 days prior to initiation of study treatment. They must be willing to use a medically approved highly effective method of contraception (e.g., intrauterine device, oral contraceptives, condoms) during the study period and for 3 months after the last dose of study drug.
• Contraception (Males): Male subjects with partners of childbearing potential must use effective methods of contraception during the study period and for 3 months after the last dose of study drug.
• Consent and Compliance: The subject has voluntarily agreed to participate by signing the ICF and is willing and able to comply with scheduled visits, study treatment, laboratory tests, and other trial procedures.

You may not qualify if:

• Distant Metastasis: Confirmed by systemic imaging (CT（Computed Tomography）, MR （Magnetic Resonance Imaging）, or PET-CT （Positron Emission Tomography - Computed Tomography）) encompassing at least the chest, abdomen, and pelvis.
• Pharmacogenetic Deficiency: Known complete DPD (dihydropyrimidine dehydrogenase) enzyme deficiency or homozygous UGT1A1\*28 (7/7) genotype identified by whole-genome testing.
• Acute Surgical Complications: Presence of complete intestinal obstruction, active bleeding, or perforation requiring emergency surgery.
• Other Active Malignancies: History or concurrent presence of other active malignancies, except for malignancies treated with curative intent with no recurrence for \>5 years, or adequately treated carcinoma in situ (e.g., cervical carcinoma in situ, non-melanoma skin cancer).
• Thromboembolic Events: History of thromboembolic events (e.g., cerebrovascular accident \[including transient ischemic attack\], pulmonary embolism, deep vein thrombosis) within 12 months prior to study enrollment.
• Significant Cardiac Disease: Occurrence of any of the following within 12 months prior to enrollment: myocardial infarction, severe/unstable angina, heart failure of NYHA （New York Heart Association Functional Classification）class 2 or higher, clinically significant supraventricular or ventricular arrhythmia requiring treatment, or symptomatic congestive heart failure.
• Recent Infection/Fever: Systemic antibiotic use for ≥7 days within 4 weeks prior to enrollment, or unexplained fever \>38.5°C during screening or prior to the first dose (fever attributed to the tumor by the investigator is allowed).
• Major Surgery/Trauma: Undergone major surgery (e.g., laparotomy, thoracotomy, organ resection via laparoscopy) or experienced significant trauma within 2 months prior to enrollment. The surgical incision must be fully healed before study entry.
• HIV/AIDS: Known HIV (Human Immunodeficiency Virus) infection or AIDS (Acquired Immunodeficiency Syndrome)-related illness.
• Significant Pulmonary/Systemic Disease: Presence of interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases (e.g., diabetes mellitus, hypertension, pulmonary fibrosis, acute pneumonitis).
• Untreated Active Hepatitis: Untreated active hepatitis B virus (defined as HBV-DNA ≥ 500 IU/mL) or hepatitis C virus (defined as HCV-RNA above the lower limit of quantification), or known co-infection with HBV and HCV.
• Drug Hypersensitivity: Known or suspected history of hypersensitivity to any of the drugs related to the study treatment.
• Investigator Discretion: Any other condition that, in the judgment of the investigator, would make the patient unsuitable for participation in the study.

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

Study Sites (1)

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

Location

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 (Alvenor) 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 (Alvenor): 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 1, 2026
• Primary Completion (Estimated): March 1, 2031
• Study Completion (Estimated): March 1, 2031
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)