Clinical trial NCT02251977: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Chemotherapy-induced Neutropenia
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2014-09-29
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: rates of grade 2 or more chronic cumulative neurotoxicity of both arms
timeFrame: 9 months
Secondary outcomes:
measure: rates of chronic cumulative neurotoxicity of both arms
timeFrame: 9 months
measure: time to grade 2 or more neurotoxicity of both arms
timeFrame: 9 months
measure: rates of dose reduction or withdrawal due to oxaliplatin induced neurotoxicity of both arms
timeFrame: 9 months
measure: rates of acute neurotoxicity of both arms
timeFrame: 6 months
measure: rates and grades of adverse reactions of both arms
timeFrame: 6 months
measure: rates of 3 year disease free survival of both arms
timeFrame: 3 years
Other outcomes:
measure: change degrees of the levels of nerve growth factor and other neurotrophic factors of both arms
timeFrame: 6 months
measure: genetic polymorphisms of oxaliplatin induced severe and cumulative neurotoxicity
timeFrame: 6 months
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Yuhong Li, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.