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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02251977
• Other study ID #: GOXL-18
• Status: Completed
• Phase: Phase 3
• Start date: September 2014
• Est. completion date: September 5, 2017

Study information

• Verified date: October 2019
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 196
• Est. completion date: September 5, 2017
• Est. primary completion date: September 5, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Chemotherapy-induced Neutropenia
• Colorectal Cancer
• Colorectal Neoplasms
• Neurotoxicity Syndromes
• Neutropenia

Intervention

Drug:
• GM1
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.
• placebo
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.
• mFOLFOX6 or XELOX
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.

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Yuhong Li

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	change degrees of the levels of nerve growth factor and other neurotrophic factors of both arms		6 months
Other	genetic polymorphisms of oxaliplatin induced severe and cumulative neurotoxicity		6 months
Primary	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	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
Secondary	time to grade 2 or more neurotoxicity of both arms		9 months
Secondary	rates of dose reduction or withdrawal due to oxaliplatin induced neurotoxicity of both arms		9 months
Secondary	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
Secondary	rates and grades of adverse reactions of both arms		6 months
Secondary	rates of 3 year disease free survival of both arms		3 years