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

Primary Purpose

Colorectal Cancer, Chemotherapy-induced Neutropenia

Status

Completed

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

GM1

placebo

mFOLFOX6 or XELOX

About this trial

This is an interventional prevention trial for Colorectal Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Sun Yat-sen University Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Adjuvant Chemotherapy plus GM1

Adjuvant Chemotherapy plus placebo

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

time to grade 2 or more neurotoxicity of both arms

rates of dose reduction or withdrawal due to oxaliplatin induced neurotoxicity of both arms

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

rates and grades of adverse reactions of both arms

rates of 3 year disease free survival of both arms

Full Information

NCT ID

NCT02251977

First Posted

September 21, 2014

Last Updated

October 3, 2019

Sponsor

Yuhong Li

1. Study Identification

Unique Protocol Identification Number

NCT02251977

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

September 2014 (undefined)

Primary Completion Date

September 5, 2017 (Actual)

Study Completion Date

September 5, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Yuhong Li

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer, Chemotherapy-induced Neutropenia

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

196 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Adjuvant Chemotherapy plus GM1

Arm Type

Experimental

Arm Description

Arm Title

Adjuvant Chemotherapy plus placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

GM1

Other Intervention Name(s)

monosialotetrahexosylganglioside

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

placebo

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

mFOLFOX6 or XELOX

Other Intervention Name(s)

Oxalipaltin, Leucovorin, Calcium Folinate, 5-Fluorouracil, Capecitabine

Intervention Description

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.

Primary Outcome Measure Information:

Title

rates of grade 2 or more chronic cumulative neurotoxicity of both arms

Description

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

Time Frame

9 months

Secondary Outcome Measure Information:

Title

rates of chronic cumulative neurotoxicity of both arms

Description

measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20

Time Frame

9 months

Title

time to grade 2 or more neurotoxicity of both arms

Time Frame

9 months

Title

rates of dose reduction or withdrawal due to oxaliplatin induced neurotoxicity of both arms

Time Frame

9 months

Title

rates of acute neurotoxicity of both arms

Description

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

Time Frame

6 months

Title

rates and grades of adverse reactions of both arms

Time Frame

6 months

Title

rates of 3 year disease free survival of both arms

Time Frame

3 years

Other Pre-specified Outcome Measures:

Title

change degrees of the levels of nerve growth factor and other neurotrophic factors of both arms

Time Frame

6 months

Title

genetic polymorphisms of oxaliplatin induced severe and cumulative neurotoxicity

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yuhong Li, MD

Organizational Affiliation

Sun Yat-sen University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sun Yat-sen University Cancer Center

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

12. IPD Sharing Statement

Citations:

PubMed Identifier

31724334

Citation

Wang DS, Wang ZQ, Chen G, Peng JW, Wang W, Deng YH, Wang FH, Zhang JW, Liang HL, Feng F, Xie CB, Ren C, Jin Y, Shi SM, Fan WH, Lu ZH, Ding PR, Wang F, Xu RH, Li YH. Phase III randomized, placebo-controlled, double-blind study of monosialotetrahexosylganglioside for the prevention of oxaliplatin-induced peripheral neurotoxicity in stage II/III colorectal cancer. Cancer Med. 2020 Jan;9(1):151-159. doi: 10.1002/cam4.2693. Epub 2019 Nov 13.

Results Reference

derived

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

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