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

Phase 3

Interventions: Drug: Mimetic granules of Yiqi-Wenjing prescriptions
Drug: Huangqi-Guizhi-Wuwu granules
Drug: Danggui-Sini granules

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Placebo-control group	Mimetic granules of Yiqi-Wenjing prescriptions	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.
Treatment group I	Huangqi-Guizhi-Wuwu granules	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.
Treatment group II	Danggui-Sini granules	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.

Primary Outcome Measures

Name	Time	Method
The dynamic change of the degree of oxaliplatin-induced peripheral neuropathy	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.	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.

Secondary Outcome Measures

Name	Time	Method
The dynamic change of quality of life	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.	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.
The number of completed chemotherapy cycles	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).	The number of completed chemotherapy cycles will be recorded. If the result is less then 6, the specific reason should be noted.
The dynamic change of the grades of oxaliplatin-induced peripheral neuropathy	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 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.