Rectal Cancer Patients, Rectal Cancer Stage II, Rectal Cancer Stage III
Conditions
Keywords
Neoadjuvant Therapy, mFOLFOX6, Citrus Flavonoid Tablets (Aimailang)
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 Patients receiving non-protocol anticancer therapies preoperatively will be withdrawn from the study.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.
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
DRUGmFOLFOX 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. Citrus flavonoid tablets (Alvenor) : 500 mg orally three times daily (Days 1-14), administered with or without the chemotherapy regimen (depending on group assignment).
DRUGmFOLFOX 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.
Sponsors
Sixth Affiliated Hospital, Sun Yat-sen University
Guangzhou First People's Hospital
Zhujiang Hospital
The First Affiliated Hospital of Guangzhou Medical University
Guangdong Provincial People's Hospital
Fujian Provincial Hospital
The Third Affiliated Hospital of Guangzhou Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Histopathologically confirmed rectal adenocarcinoma; all other histologic subtypes are excluded. Presence of hemorrhoids confirmed by colonoscopy or clinical physical examination. 2. 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). 3. 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). 4. ectal cancer tumor specimens demonstrate high YWHAB expression by immunohistochemistry. 5. Age 18-75 years at the time of informed consent. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Appendix 3). 7. No prior systemic anticancer therapy for rectal cancer, including cytotoxic chemotherapy, immune checkpoint inhibitors, molecular targeted agents, or endocrine therapy. 8. 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 9. 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. 10. Male patients with partners of childbearing potential must practice effective contraception during the study and for 3 months following the last study drug administration. 11. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor downstaging rate (to ypTNM stage 0-I) | Perioperative，2 weeks after surgery | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Three-year disease-free survival | through study completion, an average of 3 year | Disease-free survival (DFS) was defined as the proportion of patients who, from the time of randomization until the end of year 3, did not experience any of the following events: disease progression; macroscopic or microscopic residual tumor after surgery; local recurrence; distant metastasis; or death from any cause, whichever occurred first. |
| Overall survival | through study completion, an average of 5 year | Overall survival (OS) was defined as the time from randomization to death from any cause. |
| tumor regression grade (TRG) | Perioperative，2 weeks after surgery | TRG 0 indicates no residual tumor cells; TRG 1 indicates single cells or small groups of cells; TRG 2 indicates residual cancer with a desmoplastic response; and TRG 3 indicates minimal evidence of tumor response. |
| Rate of Treatment-Related Adverse Events (Grade 3 or Higher) | through study completion, an average of 1 year | Treatment-related adverse event rate (Grade ≥3): Refers to grade 3 or higher adverse drug reactions determined to be related to the investigational antineoplastic drug/treatment in clinical trials, excluding nonspecific infusion reactions. |
| Complete response (CR) rate | Perioperative，2 weeks after surgery | The proportion of patients with complete response (CR) after surgery. Complete response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. |
| Partial response (PR) rate | Perioperative，2 weeks after surgery | The proportion of patients with partial response (PR) after surgery. Partial response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Stable disease (SD) rate | Perioperative，2 weeks after surgery | The proportion of patients with stable disease (SD) after surgery. Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
| Progressive disease (PD) rate | Perioperative，2 weeks after surgery | The proportion of patients with progressive disease (PD) after surgery. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (including the baseline if that is the smallest), with an absolute increase of at least 5 mm, or the appearance of one or more new lesions. |
Countries
China
Contacts
CONTACTTuo Hu, M.D./Ph.D
PRINCIPAL_INVESTIGATORXiaosheng He, M.D./Ph.D
Sixth Affiliated Hospital, Sun Yat-sen University
Outcome results
None listed