Clinical Trial of Neoadjuvant mFOLFOX Plus Alvenor for LARC Patients With High YWHAB Expression
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorSixth Affiliated Hospital, Sun Yat-sen University
About this trial
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Patients receiving non-protocol anticancer therapies preoperatively will be withdrawn from the study.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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
None
Trial design
Design model
Parallel
Treatments tested in this trial
mFOLFOX regimen combined with Citrus Flavone Tablets (Alvenor) neoadjuvant treatment group
DrugThe 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).
mFOLFOX regimen neoadjuvant therapy group
DrugThe 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.
Treatment groups
236 Participants
are divided into 2 treatment groupsGroup A: mFOLFOX regimen neoadjuvant therapy groupActive comparator 1 intervention
Group B: mFOLFOX regimen combined with Citrus Flavone Tablets (Alvenor) neoadjuvant treatment groupExperimental treatment 1 intervention
Trial outcomes
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.
Time frame
Perioperative，2 weeks after surgerySecondary outcomes
1
Three-year disease-free survival
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.
Time frame
through study completion, an average of 3 year2
Overall survival
Overall survival (OS) was defined as the time from randomization to death from any cause.
Time frame
through study completion, an average of 5 year3
tumor regression grade (TRG)
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.
Time frame
Perioperative，2 weeks after surgery4
Rate of Treatment-Related Adverse Events (Grade 3 or Higher)
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.
Time frame
through study completion, an average of 1 yearSponsors and contacts
Click on the lead sponsor to view all of their trials.
Sixth Affiliated Hospital, Sun Yat-sen University
Lead sponsor
Guangzhou First People's Hospital
Collaborator
Zhujiang Hospital
Collaborator
The First Affiliated Hospital of Guangzhou Medical University
Collaborator
Guangdong Provincial People's Hospital
Collaborator
Fujian Provincial Hospital
Collaborator
The Third Affiliated Hospital of Guangzhou Medical University
Collaborator
Source ClinicalTrials.gov