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

NCT02251977 | Completed Phase 3 DMC

• 1 other identifier: GOXL-18
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer; Chemotherapy-induced Neutropenia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• rates of chronic cumulative neurotoxicity of both arms

  9 months

• 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

• rates and grades of adverse reactions of both arms

  6 months

Other Outcomes (2)

• 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

Study Arms (2)

Adjuvant Chemotherapy plus GM1

EXPERIMENTAL

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; Drug: mFOLFOX6 or XELOX

Adjuvant Chemotherapy plus placebo

PLACEBO COMPARATOR

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; Drug: mFOLFOX6 or XELOX

Interventions

GM1 DRUG

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.

Also known as: monosialotetrahexosylganglioside

Adjuvant Chemotherapy plus GM1

placebo DRUG

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.

Adjuvant Chemotherapy plus placebo

mFOLFOX6 or XELOX DRUG

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.

Also known as: Oxalipaltin, Leucovorin, Calcium Folinate, 5-Fluorouracil, Capecitabine

Adjuvant Chemotherapy plus GM1; Adjuvant Chemotherapy plus placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yuhong Li: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Related Publications (1)

• 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.

  PMID: 31724334 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

G(M1) Ganglioside; XELOX; Leucovorin; Fluorouracil; Capecitabine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Gangliosides; Acidic Glycosphingolipids; Glycosphingolipids; Glycolipids; Glycoconjugates; Carbohydrates; Lipids; Sphingolipids; Membrane Lipids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Yuhong Li, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD Ph D

Study Record Dates

• First Submitted: September 21, 2014
• First Posted: September 29, 2014
• Study Start: September 1, 2014
• Primary Completion: September 5, 2017
• Study Completion: September 5, 2017
• Last Updated: October 7, 2019

Record last verified: 2019-10

Locations

CN (1)