Effect of GM1 in Prevention of Oxaliplatin Induced Neurotoxicity in Stage II/III Colorectal Cancer

Study Overview
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Brief Summary
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The primary objective of this study is to assess the efficacy of monosialotetrahexosylganglioside (GM1) for preventing oxaliplatin induced neurotoxicity in colorectal cancer patients who received oxaliplatin-based adjuvant chemotherapy.

Detailed Description
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Oxaliplatin is a key agent in the treatment of colorectal cancer. However, peripheral neuropathy markedly limits the use of oxaliplatin. Many drugs have been tried to decrease the development of oxaliplatin induced peripheral neurotoxicity, however, the results remain disappointing. This multi-center, randomized, placebo-controlled trial was performed to assess the efficacy of monosialotetrahexosylganglioside (GM1) for preventing oxaliplatin induced neurotoxicity in colorectal cancer patients who received oxaliplatin-based adjuvant chemotherapy.

Official Title
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The Effect of Monosialotetrahexosylganglioside (GM1) in Prevention of Oxaliplatin Induced Neurotoxicity in Colorectal Cancer Patients Who Received Oxaliplatin-based Adjuvant Chemotherapy: A Multi-center, Randomized, Placebo-controlled Trial

Conditions
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Colorectal Cancer, Chemotherapy-induced Neutropenia

Intervention / Treatment
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* Drug: GM1
* Drug: placebo
* Drug: mFOLFOX6 or XELOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-75 years old, male or female Histologically confirmed diagnosis of colorectal adenocarcinoma with a phase II or III disease, within 2 months from radical resection, and intends to receive 6 months of adjuvant chemotherapy with mFOLOFX6 or XELOX, without adjuvant radiation indications No prior any level of peripheral nerve system disease Patients have not received any other possible neurotoxic-reaction-causing drugs (such as oxaliplatin, cisplatin and paclitaxel drugs etc) With the capability to accurately record the occurrence and severity of neurotoxicity by questionnaire With normal functions of major organs No contraindication to chemotherapy Life expectancy ≥ 3 months Patients have provided a signed Informed Consent Form Exclusion Criteria: Patients who received radical resection, but are expected not be able to complete 6 months of adjuvant chemotherapy Patients who receive palliative chemotherapy Patients who need adjuvant or palliative radiotherapy during chemotherapy Be allergic to GM1 Hereditary abnormal metabolism of glucose and lipid Doctors believe that patients are not suitable for receiving GM1 treatment With confirmed history of neurological or psychiatric disorders, including epilepsy and dementia With concomitant diseases that will seriously harm the patients' safety or impact the completion of the study Patients (male or female) have fertility possibility but not willing or not to take effective contraceptive measures

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adjuvant Chemotherapy plus GM1<br>Patients will receive mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) or XELOX (capecitabine and oxaliplatin) for adjuvant chemotherapy. While GM1 will be delivered to patients through the day before the initiation of chemotherapy (Day0) to the completion of chemotherapy (Day4), and the dosages of GM1 for patients who receive mFOLFOX6 or XELOX are 80mg or 120mg per day. | Drug: GM1<br>* GM1 will be delivered to patients through the day before the initiation of chemotherapy (Day0) to the completion of chemotherapy (Day4), and the dosages of GM1 for patients who receive mFOLFOX6 or XELOX are 80mg or 120mg per day.<br>* Other names: monosialotetrahexosylganglioside;Drug: mFOLFOX6 or XELOX<br>* mFOLFOX6: Patients will receive mFOLFOX6 every 14 days, Oxaliplatin 85mg/m2 IV over 3 hours on Day1; Calcium Folinate IV over 2h on Day 1(Leucovorin 200mg/m2 or CF 400 mg/m2); 5-Fluorouracil 400mg/m2 IV on Day1; followed by 5-Fluorouracil 2.4g/m2 for 46 hours continuous infusion on Day1. XELOX: Patients will receive XELOX every 21 days, Oxaliplatin 130mg/m2 IV over 3 hours on Day1;followed by Capecitabine 1000mg/m2 oral twice daily for 14 days. The optimum chemotherapy regimen is at the discretion of the investigators based on the condition of each patient.<br>* Other names: Capecitabine;|
| Placebo Comparator: Adjuvant Chemotherapy plus placebo<br>Patients will receive mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) or XELOX (capecitabine and oxaliplatin) for adjuvant chemotherapy. While placebo will be delivered to patients through the day before the initiation of chemotherapy (Day0) to the completion of chemotherapy (Day4). | Drug: placebo<br>* Placebo will be delivered to patients through the day before the initiation of chemotherapy (Day0) to the completion of chemotherapy (Day4), and the dosages of placebo for patients who receive mFOLFOX6 or XELOX are 80mg or 120mg per day.<br>Drug: mFOLFOX6 or XELOX<br>* mFOLFOX6: Patients will receive mFOLFOX6 every 14 days, Oxaliplatin 85mg/m2 IV over 3 hours on Day1; Calcium Folinate IV over 2h on Day 1(Leucovorin 200mg/m2 or CF 400 mg/m2); 5-Fluorouracil 400mg/m2 IV on Day1; followed by 5-Fluorouracil 2.4g/m2 for 46 hours continuous infusion on Day1. XELOX: Patients will receive XELOX every 21 days, Oxaliplatin 130mg/m2 IV over 3 hours on Day1;followed by Capecitabine 1000mg/m2 oral twice daily for 14 days. The optimum chemotherapy regimen is at the discretion of the investigators based on the condition of each patient.<br>* Other names: Capecitabine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rates of grade 2 or more chronic cumulative neurotoxicity of both arms | measured by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0, with standardized questions regarding neurotoxic symptoms and examples of answers | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rates of chronic cumulative neurotoxicity of both arms | measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 | 9 months | 
| time to grade 2 or more neurotoxicity of both arms |  | 9 months | 
| rates of dose reduction or withdrawal due to oxaliplatin induced neurotoxicity of both arms |  | 9 months | 
| rates of acute neurotoxicity of both arms | measured by a numerical analog scale ranging from 0 to 10 that addressed sensitivity touching cold items, discomfort swallowing cold items, throat discomfort, and muscle cramps | 6 months | 
| rates and grades of adverse reactions of both arms |  | 6 months | 
| rates of 3 year disease free survival of both arms |  | 3 years |