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

Sponsor

Yuhong Li (Other)

Overall Status

Completed

CT.gov ID

NCT02251977

Collaborator

(none)

196

Enrollment

Location

Arms

36.1

Duration (Months)

5.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Chemotherapy-induced Neutropenia	Drug: GM1 Drug: placebo Drug: mFOLFOX6 or XELOX	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

196 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

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

Study Start Date :

Sep 1, 2014

Actual Primary Completion Date :

Sep 5, 2017

Actual Study Completion Date :

Sep 5, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Adjuvant Chemotherapy plus 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.	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. Other Names: monosialotetrahexosylganglioside Drug: 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. Other Names: Oxalipaltin Leucovorin Calcium Folinate 5-Fluorouracil Capecitabine
Placebo Comparator: Adjuvant Chemotherapy plus 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).	Drug: 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. Drug: 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. Other Names: Oxalipaltin Leucovorin Calcium Folinate 5-Fluorouracil Capecitabine

Arm

Intervention/Treatment

Experimental: Adjuvant Chemotherapy plus 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.

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.

Other Names:

monosialotetrahexosylganglioside

Drug: 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.

Other Names:

Oxalipaltin

Leucovorin

Calcium Folinate

5-Fluorouracil

Capecitabine

Placebo Comparator: Adjuvant Chemotherapy plus 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).

Drug: 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.

Drug: mFOLFOX6 or XELOX

Other Names:

Oxalipaltin

Leucovorin

Calcium Folinate

5-Fluorouracil

Capecitabine

Outcome Measures

Primary Outcome Measures

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

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 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
rates and grades of adverse reactions of both arms [6 months]
rates of 3 year disease free survival of both arms [3 years]

Other Outcome Measures

change degrees of the levels of nerve growth factor and other neurotrophic factors of both arms [6 months]
genetic polymorphisms of oxaliplatin induced severe and cumulative neurotoxicity [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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