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

Phase 3

Completed

• Conditions: Colorectal Cancer; Chemotherapy-induced Neutropenia
• Interventions: Drug: placebo; Drug: GM1; Drug: mFOLFOX6 or XELOX

• Registration Number: NCT02251977
• Lead Sponsor: Yuhong Li

Brief Summary

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

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.

Study Timeline

• Study Start: 2014-09
• Study First Submitted: 2014-09-21
• Study First Submitted QC: 2014-09-25
• Study First Posted: 2014-09-29
• Primary Completion: 2017-09-05
• Study Completion: 2017-09-05
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-03
• Last Update Posted: 2019-10-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 196

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Adjuvant Chemotherapy plus GM1	mFOLFOX6 or XELOX	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.
Adjuvant Chemotherapy plus placebo	placebo	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).
Adjuvant Chemotherapy plus placebo	mFOLFOX6 or XELOX	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).
Adjuvant Chemotherapy plus GM1	GM1	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.

Primary Outcome Measures

Name	Time	Method
rates of grade 2 or more chronic cumulative neurotoxicity of both arms	9 months	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

Secondary Outcome Measures

Name	Time	Method
rates of 3 year disease free survival of both arms	3 years
rates of chronic cumulative neurotoxicity of both arms	9 months	measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20
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 and grades of adverse reactions of both arms	6 months
rates of acute neurotoxicity of both arms	6 months	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

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China