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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 236
- 试验地点
- 1
- 主要终点
- Tumor downstaging rate (to ypTNM stage 0-I)
研究概览
简要总结
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Patients receiving non-protocol anticancer therapies preoperatively will be withdrawn from the study.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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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, M
- •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.
排除标准
- •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.
研究组 & 干预措施
mFOLFOX regimen neoadjuvant therapy group
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
干预措施: mFOLFOX regimen neoadjuvant therapy group (Drug)
mFOLFOX regimen combined with Citrus Flavone Tablets (Alvenor) neoadjuvant treatment group
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).
干预措施: mFOLFOX regimen combined with Citrus Flavone Tablets (Alvenor) neoadjuvant treatment group (Drug)
结局指标
主要结局
Tumor downstaging rate (to ypTNM stage 0-I)
时间窗: 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.
次要结局
- 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)
- Partial response (PR) rate(Perioperative，2 weeks after surgery)
- Stable disease (SD) rate(Perioperative，2 weeks after surgery)
- Progressive disease (PD) rate(Perioperative，2 weeks after surgery)