The Efficacy and Safety of Mecobalamin in the Prevention of Capecitabine Induced Hand Foot Syndrome

Study Overview
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Brief Summary
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A multicenter, randomized, placebo-controlled, double-blind, phase III clinical trial will be conducted to explore the efficacy and safety of mecobalamin in the prevention of 2/3 HFS in patients with early breast cancer. 234 patients will be enrolled and will be randomized into mecobalamin group and placebo group at the ration of 1:1. The incidence of grade 2 / 3 HFS in the experimental group and the control group will be observed. This study is expected to provide evidence for clinical prevention of hand foot syndrome, improve clinical treatment guidelines for early breast cancer, and provide reference for other antitumor drugs for hand foot syndrome.

Detailed Description
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Capecitabine is a drug recommended for adjuvant therapy in early breast cancer. The key to improving the prognosis of early breast cancer is to ensure that adequate treatment is sufficient. Hand foot syndrome Hand foot syndrome (HFS) is the most common and specific side effect of capecitabine, in which the incidence of grade 2 / 3 HFS requiring treatment is as high as 17-36%. At present, there is no specific drug for the treatment of HFS, and capecitabine must be reduced or stopped in case of grade 2 / 3 HFS. The guidelines also do not recommend standard drugs for the prevention of HFS. Mecobalamin is a derivative of vitamin B12, which can improve autonomic nervous system After symptoms and repair of small neuropathy, its clinical indication is the treatment of peripheral neuropathy. A multicenter, randomized, placebo-controlled, double-blind, phase III clinical trial will be conducted to explore the efficacy and safety of mecobalamin in the prevention of 2/3 HFS in patients with early breast cancer. 234 patients will be enrolled and will be randomized into mecobalamin group and placebo group at the ration of 1:1. The incidence of grade 2 / 3 HFS in the experimental group and the control group will be observed. This study is expected to provide evidence for clinical prevention of hand foot syndrome, improve clinical treatment guidelines for early breast cancer, and provide reference for other antitumor drugs for hand foot syndrome.

Official Title
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The Efficacy and Safety of Mecobalamin in the Prevention of Capecitabine Induced Hand Foot Syndrome in Breast Cancer Patients: A Multicenter, Phase III, Randomized, Double-blind, Controlled Trial

Conditions
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Hand-foot Syndrome

Intervention / Treatment
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* Drug: Mecobalamin 5 MG Disintegrating Oral Tablet
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female, aged 18 to 75 Her-2 negative patients with non metastatic breast cancer. patients with early breast cancer who did not receive PCR after neoadjuvant chemotherapy or patients with lymph node metastasis after breast cancer surgery. Prepare to receive postoperative adjuvant single drug capecitabine or capecitabine combined with endocrine therapy and / or radiotherapy The Binbin dose is 1000mg / ㎡, bid (continuous oral administration for 14 days, stopping for 7 days, repeated every 21 days) Eastern cancer cooperation group (ECoG) physical strength score 0-1; During randomization, the toxicity related to previous treatment must be alleviated to NCI CTCAE (version 4.03) ≤ 1 degree (except hair loss or according to the research) Other toxicity judged by the investigator that there is no risk to the safety of the patient); Blood routine examination was basically normal within 4 weeks before enrollment: A. white blood cell count (WBC) ≥ 3.0 × 10 ^ 9 / L, B. medium Sex granulocyte count (ANC) ≥ 1.5 × 10 ^ 9 / L, C. platelet count (PLT) ≥ 100 × 10^9／L; The liver and kidney function tests were basically normal within 4 weeks before enrollment (based on the normal values in the laboratories of each research center): a Total bilirubin (TBIL) ≤ 1.5 × Upper limit of normal value (ULN), B. alanine aminotransferase and aspartate aminotransferase (ALT / AST) ≤2.5 × ULN (patients with liver metastasis) ≤ 5 × ULN), C. serum creatinine ≤ 1.5 × ULN or creatinine clearance (CCR) ≥60 ml/min； Women of childbearing age must have a serum / urine pregnancy test 4 weeks before enrollment, and the result is negative, and are willing to participate in the study Use a medically recognized high-efficiency contraceptive during and within 6 months after the last administration of the drug; Informed consent has been signed before joining the group; There was no active infectious disease within 12 weeks of screening period Exclusion Criteria: in the first 5 years of randomised allocation, there was a history of malignancy except for breast cancer, but the risk of metastasis or death was negligible. Except for malignant tumors that can be cured after treatment (such as appropriately treated cervical carcinoma in situ, non melanoma skin cancer or stage I cancer) Uterine cancer, thyroid cancer, etc.); Any accompanying disease or condition that may interfere with the study, or any serious medical impairment that may affect the safety of the subject (for example, uncontrollable heart disease, hypertension, active or uncontrollable infection, active hepatitis B virus infection); there are diseases affecting skin: diabetes, dermatomyositis, sclerosing disease, lupus erythematosus and so on. Known history of psychotropic substance abuse or drug abuse; Pregnant or lactating patients; Inability to swallow, intestinal obstruction or other factors affecting drug administration and absorption.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mecobalamin group<br>Mecobalamin (0.5mg / time, 3 times / day) for 6 months | Drug: Mecobalamin 5 MG Disintegrating Oral Tablet<br>* Mecobalamin 0.5mg / time, 3 times / day,was taken continuously for 6 months<br>|
| Placebo Comparator: Placebo group<br>placebo (0.5mg / time, 3 times / day) for 6 months | Drug: placebo<br>* placebo 0.5mg / time, 3 times / day,was taken continuously for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of grade 2 / 3 hand foot syndrome | The incidence equals the numbers of patients happens 2nd or 3rd level hand foot syndrome/the number of total patients in each group | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The reduction or withdrawal rate of capecitabine | the proportion of subjects with capecitabine reduction of more than 75% or capecitabine withdrawal accounted for the proportion of subjects in each group | 6 months | 
| Disease Free Survival | The time from the beginning of treatment to the recurrence of the disease or death from any cause or the end of the visit | 5 years | 
| Overall Survival | The time from the beginning of treatment to the death of the patient caused by any factor | 5 year | 
| The score of life quality questionnaire | The score of HF-Qol | 6 months | 
| The score of life quality | The score of QLQ-C30 | 6 months | 
| The score of life quality QLQ-BR23 | The score of QLQ-BR23 | 6 months | 
| The incidence of adverse events | Incidence of adverse outcome events (such as fatigue, malignancy / vomiting, abdominal pain, diarrhea, stomatitis, impaired liver function, bone marrow suppression, etc.) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hand-foot Syndrome, Mecobalamin, Capecitabine, Breast Cancer