Yiqi Wenjing Prescriptions Preventive Efficacy of Oxaliplatin-induced Peripheral Neuropathy Clinical Trial

Study Overview
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Brief Summary
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This study is a randomized, placebo-controlled, double-blind, multicenter phase III clinical trial of Yiqi Wenjing prescriptions for Preventing Oxaliplatin-induced Peripheral Neuropathy.

Detailed Description
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This study is a randomized, placebo-controlled, double-blind, and multicenter clinical trial. Three hundred sixty postoperative patients with colon cancer stage IIa-IIIc will be randomly assigned into treatment group I, treatment group II and placebo-control group, taking Huangqi Guizhi Wuwu granules, Danggui Sini granules and the mimetic granules of Yiqi Wenjing granules respectively. All subjects will receive mFOLFOX6 or FOLFOX4 or XELOX chemotherapy regimen along with traditional Chinese medicine(TCM) or placebo treatment per day for at least three months and one year follow up. EORTC QLQ-CIPN20 will be used to assess the degree of peripheral neuropathy as the primary outcome measure. Grades of OIPN evaluated by NCI-CTCAE 5.0, quality of life evaluated by EORTC QLQ-C30, chemotherapeutic efficacy evaluated by RESIST 1.1, and the number of completed chemotherapy cycles are selected as the secondary outcome measures.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase Ⅲ Clinical Trial of Yiqi Wenjing Prescriptions for Preventing Oxaliplatin-induced Peripheral Neuropathy

Conditions
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Chemotherapy-induced Peripheral Neuropathy, Colorectal Cancer

Intervention / Treatment
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* Drug: Mimetic granules of Yiqi-Wenjing prescriptions
* Drug: Huangqi-Guizhi-Wuwu granules
* Drug: Danggui-Sini granules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject diagnosed with colorectal cancer stages IIa-IIIc, confirmed by histopathological examination, according to CSCO guidelines for diagnosis and treatment of colorectal cancer. Subject suitable for receiving FOLFOX4 or mFOLFOX6 as adjuvant chemotherapy after radical resection of colorectal cancer, receiving each dose and cumulative dose of oxaliplatin are 85mg/m2 and ≥540 mg/m2 respectively. Subject with Karnofsky performance status scale (Schag et al.1984) index ≥60 points and an expected survival time ≥6 months. Subject over 18 years of age, men or women. Subject without severe damage of the heart, liver, kidney or hematopoietic system. Exclusion Criteria: Subject with any grade of peripheral neuropathy. Subject who has ever received treatment of neurotoxic chemotherapeutics, such as oxaliplatin, cisplatin, taxanes, or vinca alkaloids. Subject who is receiving agents with potential preventive or therapeutic effects to neuropathy, such as duloxedine, carbamazepine, venlafaxine, gabapentin, pregabalin, phenytoin, valproate, milnacipran, or tricyclic antidepressant. Subject who is participating or have participated in other clinical trials. Subject with a family history of hereditary/familial neuropathy. Subject who cannot take drugs orally. Subject with mental illness who cannot cooperate. Pregnant or lactation period women.

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subject diagnosed with colorectal cancer stages IIa-IIIc, suitable for receiving FOLFOX4 or mFOLFOX6 as adjuvant chemotherapy after radical resection of colorectal cancer, receiving each dose and cumulative dose of oxaliplatin are 85mg/m2 and ≥540 mg/m2 respectively, with Karnofsky performance status scale (Schag et al.1984) index ≥60 points and an expected survival time ≥6 months, over 18 years of age, men or women, without severe damage of the heart, liver, kidney or hematopoietic system.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo-control group<br>Subjects will receive FOLFOX4 or mFOLFOX6 or XELOX chemotherapy regimen and placebo treatment twice a day (1/2 bag, morning and evening) for at least three months and one year follow up. | Drug: Mimetic granules of Yiqi-Wenjing prescriptions<br>* The intervention relates to a multiple granules, which contains 2.5% concentrated Huangqi-Guizhi-Wuwu decoction (a classical traditional Chinese prescription consists of astragalus membranaceus, cassia twig, radix paeoniae alba, ginger and jujube), 2.5% concentrated Danggui-Sini decoction (a classical traditional Chinese prescription consists of angelica sinensis, cassia twig, radix paeoniae alba, asarum, tetrapanax papyriferus, jujube and honey-fried licorice root), bitter principle, food colouring and starch.<br>* Other names: Mimetic granules of Huangqi-Guizhi-Wuwu plus Danggui-Sini decoction;|
| Experimental: Treatment group I<br>Subjects will receive FOLFOX4 or mFOLFOX6 or XELOX chemotherapy regimen and orally take Huangqi Guizhi Wuwu granules twice a day (1/2 bag, morning and evening) for at least three months and one year follow up. | Drug: Huangqi-Guizhi-Wuwu granules<br>* The intervention relates to a traditional Chinese prescription granules, which contains astragalus membranaceus, cassia twig, radix paeoniae alba, ginger and jujube.<br>|
| Experimental: Treatment group II<br>Subjects will receive FOLFOX4 or mFOLFOX6 or XELOX chemotherapy regimen and orally take Danggui Sini granules twice a day (1/2 bag, morning and evening) for at least three months and one year follow up. | Drug: Danggui-Sini granules<br>* The intervention relates to a traditional Chinese prescription granules, which contains angelica sinensis, cassia twig, radix paeoniae alba, asarum, tetrapanax papyriferus, jujube and honey-fried licorice root.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The dynamic change of the degree of oxaliplatin-induced peripheral neuropathy | The degree of oxaliplatin-induced peripheral neuropathy will be evaluated according to the score of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty item scale(EORTC QLQ-CIPN20, 20-80 scores, higher scores mean a worse outcome), which is graded by the subject. In order to observe the dynamic change of OIPN, this trial sets multiple measure time points. | On 1 day before and 3 days after the beginning of each cycle(each FOLFOX4 or mFOLFOX6 cycle is 14 days, each XELOX cycle is 21 days) up to Cycle 6, 1 month after the end of Cycle 6, and then every 3 months up to 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The dynamic change of the grades of oxaliplatin-induced peripheral neuropathy | The grades of oxaliplatin-induced peripheral neuropathy will be evaluated according to the grades of National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE 5.0, 0-5 grades, higher grade means a worse outcome), which is graded by the doctor. In order to observe the dynamic change of OIPN, this trial sets multiple measure time points. | On 1 day before the beginning of each cycle(each FOLFOX4 or mFOLFOX6 cycle is 14 days, each XELOX cycle is 21 days) up to Cycle 6. | 
| The dynamic change of quality of life | Quality of life will be evaluated according to the score of European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30, 28-112 scores, higher scores mean a worse outcome). In order to observe the dynamic change of QOL, this trial sets multiple measure time points. | On 1 day before the beginning of each cycle(each FOLFOX4 or mFOLFOX6 cycle is 14 days, each XELOX cycle is 21 days) up to Cycle 6. | 
| The number of completed chemotherapy cycles | The number of completed chemotherapy cycles will be recorded. If the result is less then 6, the specific reason should be noted. | At the end of Cycle 6 or after the last chemotherapy(each FOLFOX4 or mFOLFOX6 cycle is 14 days, each XELOX cycle is 21 days). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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clinical trial, Yiqi Wenjing prescriptions, oxaliplatin-induced peripheral neuropathy, randomized, placebo-controlled