Clinical Trial of Qizhu Yuling Prescription in the Prevention and Treatment of Esophagus 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 Qizhu Yuling prescription for postoperative esophagus cancer.

Detailed Description
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This study include a multi-center, randomized, double-blind, placebo, parallel controlled clinical trial.The randomized clinical trial will enroll approximately 310 patients. Participants will be randomly divided into experimental (n=155) and placebo groups (n=155).Patients in the experimental group was treated with Qizhu Yuling prescription within 6 months after esophagus cancer R0. Patients in the control group will receive the placebo.The primary endpoint is 1-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 1 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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Qizhu Yuling Prescription in the Prevention and Treatment of Postoperative Metastasis and Recurrence of Esophagus Cancer：A Randomized, Double-blind, Controlled and Multi-center Clinical Study

Conditions
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Esophagus Cancer

Intervention / Treatment
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* Drug: Qizhu Yuling Prescription
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Esophageal cancer without esophagogastric junction pT1-4aN + M0 (stage IIB-IVA) meeting the diagnostic criteria without recurrence or metastasis; 2. Patients who have completed adjuvant therapy (including adjuvant radiotherapy, adjuvant chemotherapy, adjuvant chemotherapy + radiotherapy) within 6 months after R0 resection for esophageal cancer; 3. ECOG score 0-2; 4. 18-75 years old; 5. Expected survival ≥ 3 months; 6. Subjects voluntarily signed informed consent. Exclusion Criteria: 1. Combined with primary tumor at other sites; 2. Patients complicated with severe primary diseases of heart, cerebral vessels, liver, kidney and hematopoietic system; 3. Patients with mental illness and mental and language disorders; 4. Participation in other clinical trials within 3 months; 5. Patients with known hypersensitivity or intolerance to 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Qizhu Yuling Prescription<br>Qizhu Yuling Prescription | Drug: Qizhu Yuling 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 esophageal cancer surgery.<br>|
| Placebo Comparator: Placebo Comparator<br>Simulation agent of Qizhu Yuling Prescription Group | Drug: Placebo<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 esophageal cancer surgery.<br>* Other names: Simulation agent of Qizhu Yuling Prescription;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year disease-free survival rate | Refers to the proportion of patients who did not experience recurrence, metastasis or death (from any cause) within 1 years after surgery. | The day of surgery until the first 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 | 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 | SCC | 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 | CYFR21-1 | 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 | 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 LMR | The ratio of lymphocytes to monocytes (LMR) | 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 LNR | The 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 (QLQ-QES18) | The score will be measured by Quality of Life Questionnaire of Oesophageal-Specific Module 18. Each question is scored from 1 to 4 with 18 questions giving a total score of 18 to 72. 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 (MDASI-TCM) | The score will be measured with M. D. Anderson Symptom Traditional Chinese Medicine. Each question is scored from 0 to 10 with 26 questions for a total score of 0 to 260. 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. | aseline 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 esophagus cancer, Qizhu Yuling prescription, Chinese Herbal Medicine, Randomized Controlled Trial, 1-year disease-free survival rate