Clinical Trial of Yiqi Wenyang Jiedu Prescription in the Prevention and Treatment of Postoperative Metastasis and Recurrence of Gastric Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of Yiqi Wenyang Jiedu prescription for postoperative gastric cancer.

Detailed Description
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This study include a multicenter, randomized, double-blind, placebo, parallel controlled clinical trial.The randomized clinical trial will enroll approximately 212 patients. Participants will be randomly divided into experimental (n=106) and control groups (n=106).Patients in the experimental group was treated with Yiqiuyang Jiedu prescription within 6-8 months after radical gastroctomy and after the completion of standard regimen (XELOX and SOX) for at least 6 cycles of adjuvant chemotherapy. Patients in the control group will receive the placebo.The primary endpoint is 2-year DFS (Disease-free survival) rate after surgery, that refers to the proportion of patients who do not have recurrence, metastasis or death (from any cause) within 2 years after surgery. The research protocol was approved by the relevant ethics committees, and the study was conducted according to the Declaration of Helsinki and Good Clinical Practice guidelines. Patients gave written informed consent to participate in the trial.

Official Title
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Yiqi Wenyang Jiedu Prescription in the Prevention and Treatment of Postoperative Metastasis and Recurrence of Gastric Cancer：A Randomized, Double-blind, Controlled and Multi-center Clinical Study

Conditions
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Gastric Carcinoma

Intervention / Treatment
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* Drug: Yiqi Wenyang Jiedu prescription
* Drug: Simulation agent of Yiqi Wenyang Jiedu prescription


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The non-esophagogastric junction gastric cancer of stage II-III that met the diagnostic criteria, and no tumor recurrence and metastasis was determined by imaging; Within 6-8 months after radical gastrectomy for gastric cancer (R0), adjuvant chemotherapy of standard regimen (XELOX and SOX) has been completed for at least 6 cycles; ECOG score 0-2; 18-75 years old, male or female; The expected survival time is ≥3 months; Voluntary participation in the study, signing informed consent, good compliance with follow-up. Exclusion Criteria: Patients with other primary tumors; Gastric cancer patients were pathologically diagnosed as adenosquamous carcinoma, with lymphoid stromal carcinoma (medullary carcinoma), hepatoid adenocarcinoma, squamous cell carcinoma, signed-ring cell carcinoma, undifferentiated carcinoma, gastric neuroendocrine tumor, gastric mesenchymal tumor, gastric malignant lymphoma and other gastric malignancies; Patients who had previously received preoperative neoadjuvant chemotherapy; Patients with past or current targeted drug therapy; Patients undergoing previous or ongoing gastric radiotherapy; Patients with past or ongoing tumor immunotherapy; Mental patients; Patients with serious and uncontrolled organic diseases or infections, such as decompensated heart, lung and renal failure, which lead to intolerance of chemotherapy; Patients who received clinical trials of small molecule drugs within 28 days or large molecule drugs within 3 months; Patients who are known to be allergic or intolerant to the study drug.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Yiqi Wenyang Jiedu prescription Group<br> | Drug: Yiqi Wenyang Jiedu prescription<br>* The dosage form of the test drug is granule. Patients need to take 2 small packets in the morning and 2 small packets in the evening. The medicine needs to be melted in hot water before being taken. Every 4 weeks is a course of treatment, a total of 6 courses,The patients were followed up to 3 years after gastric cancer surgery.<br>|
| Placebo Comparator: Simulation agent of Yiqi Wenyang Jiedu prescription Group<br> | Drug: Simulation agent of Yiqi Wenyang Jiedu prescription<br>* It is prepared from maltodextrin and food coloring. The raw materials of maltodextrin conform to the relevant provisions of excipients - maltodextrin in the fourth part of Chinese Pharmacopoeia 2015 edition. Food coloring includes caramel coloring, egg yolk coloring and milk chocolate brown pigment, all of which are edible grade ingredients. Patients need to take 2 small packets in the morning and 2 small packets in the evening. The medicine needs to be melted in hot water before being taken. Every 4 weeks is a course of treatment, a total of 6 courses,The patients were followed up to 3 years after gastric cancer surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year disease-free survival rate | Refers to the proportion of patients who did not experience recurrence, metastasis or death (from any cause) within 2 years after surgery. | The day of surgery until the second year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | It is the time from randomization to tumor progression or death (from any cause). | Randomization until disease recurrence, metastasis, death (from any cause) , or 36 months after surgery, whichever occurs first. | 
| Overall survival | It is the time from randomization to death (from any cause). | Randomization until death (from any cause) or 36 months after surgery, whichever occurs first. | 
| Cumulative annual recurrence and metastasis rate for 1-3 years | Refers to the proportion of patients with recurrence and metastasis within 1-3 years from the day of surgery. | The day of surgery until the once, second and third year. | 
| Cumulative annual survival rate for 1-3 years | Refers to the proportion of patients with survical within 1-3 years from the day of surgery. | The day of surgery until the once, second and third year. | 
| Indexes related to fat distribution | Total Fat Area, Visceral Fat Area and Subcutaneous Fat Area. They measure fat area on cross-sectional images using plain CT scanning. | before and after every third cycles of treatment (each cycle is 28 days), assessed up to recurrence and metastasis (up to 3 years after surgery). | 
| Visceral Adiposity Index | It is a new assessment of visceral fat based on waist circumference (WC), BMI, triglyceride (TG) and HDL. Male VAI = during [WC/(39.68 + 1.88 x BMI)] * (TG / 1.03) * (1.31 / HDL). Female VAI = during [WC/(36.58 + 1.89 x BMI)] * (TG / 0.81) * (1.52 / HDL). | before and after every third cycles of treatment (each cycle is 28 days), assessed up to recurrence and metastasis (up to 3 years after surgery). | 
| Tumor marker | CEA, CA724 and CA199 | before and after every third cycles of treatment (each cycle is 28 days), assessed up to recurrence and metastasis (up to 3 years after surgery). | 
| Peripheral blood inflammatory index | The ratio of lymphocytes to monocytes (LMR) and ratio of Lymphocyte to neutrophil ratio (LNR) | before and after every third cycles of treatment (each cycle is 28 days), assessed up to recurrence and metastasis (up to 3 years after surgery). | 
| Prognostic nutritional index | Serum albumin level (g/L) +5× total number of peripheral blood lymphocytes (×10 ^ 9 /L) | before and after every third cycles of treatment (each cycle is 28 days), assessed up to recurrence and metastasis (up to 3 years after surgery). | 
| Quality of life of the patient | This will be measured with Quality of Life Questionnaire of Stomach22 (QLQ-STO22). The minimum score is 22 and the maximum is 88. A higher score indicates a poorer quality of life. | Before and after every cycle of treatment (each cycle is 28 days), assessed up to death or 3 years after surgery. | 
| Evaluation of the patient's symptoms | This will be measured with M. D. Anderson Symptom Inventory (MDASI-GI) and Postgastrectomy Syndrome Assessment Scale (PGSAS-45). The minimum score of MDASI-GI is 0 and the maximum is 240. The minimum score of PGSAS-45 is 0 and the maximum is 271. A higher score indicates a poorer symptom. | Before and after every cycle of treatment (each cycle is 28 days), assessed up to death or 3 years after surgery. | 
| Medication compliance | The number of cases and percentage were calculated as < 80%, 80-120% and > 120% | From randomization to the end of the sixth course of medication （up to 24 weeks）. | 
| Percentage of Participants With Adverse Events | Percentage of Participants With Adverse Events in different arms. | Baseline until disease progression, death, or assessed up to 36 months after surgery. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postoperative gastric cancer, Yiqi Wenyang Jiedu prescription, Chinese Herbal Medicine, Randomized Controlled Trial, 2-year disease-free survival rate