<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02251977</url>
  </required_header>
  <id_info>
    <org_study_id>GOXL-18</org_study_id>
    <nct_id>NCT02251977</nct_id>
  </id_info>
  <brief_title>Effect of GM1 in Prevention of Oxaliplatin Induced Neurotoxicity in Stage II/III Colorectal Cancer</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yuhong Li</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to assess the efficacy of&#xD;
      monosialotetrahexosylganglioside (GM1) for preventing oxaliplatin induced neurotoxicity in&#xD;
      colorectal cancer patients who received oxaliplatin-based adjuvant chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Oxaliplatin is a key agent in the treatment of colorectal cancer. However, peripheral&#xD;
      neuropathy markedly limits the use of oxaliplatin. Many drugs have been tried to decrease the&#xD;
      development of oxaliplatin induced peripheral neurotoxicity, however, the results remain&#xD;
      disappointing. This multi-center, randomized, placebo-controlled trial was performed to&#xD;
      assess the efficacy of monosialotetrahexosylganglioside (GM1) for preventing oxaliplatin&#xD;
      induced neurotoxicity in colorectal cancer patients who received oxaliplatin-based adjuvant&#xD;
      chemotherapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">September 5, 2017</completion_date>
  <primary_completion_date type="Actual">September 5, 2017</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>rates of grade 2 or more chronic cumulative neurotoxicity of both arms</measure>
    <time_frame>9 months</time_frame>
    <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</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>rates of chronic cumulative neurotoxicity of both arms</measure>
    <time_frame>9 months</time_frame>
    <description>measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to grade 2 or more neurotoxicity of both arms</measure>
    <time_frame>9 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>rates of dose reduction or withdrawal due to oxaliplatin induced neurotoxicity of both arms</measure>
    <time_frame>9 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>rates of acute neurotoxicity of both arms</measure>
    <time_frame>6 months</time_frame>
    <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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>rates and grades of adverse reactions of both arms</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>rates of 3 year disease free survival of both arms</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>change degrees of the levels of nerve growth factor and other neurotrophic factors of both arms</measure>
    <time_frame>6 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>genetic polymorphisms of oxaliplatin induced severe and cumulative neurotoxicity</measure>
    <time_frame>6 months</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">196</enrollment>
  <condition>Colorectal Cancer</condition>
  <condition>Chemotherapy-induced Neutropenia</condition>
  <arm_group>
    <arm_group_label>Adjuvant Chemotherapy plus GM1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Adjuvant Chemotherapy plus placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GM1</intervention_name>
    <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.</description>
    <arm_group_label>Adjuvant Chemotherapy plus GM1</arm_group_label>
    <other_name>monosialotetrahexosylganglioside</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <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.</description>
    <arm_group_label>Adjuvant Chemotherapy plus placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>mFOLFOX6 or XELOX</intervention_name>
    <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.&#xD;
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.&#xD;
The optimum chemotherapy regimen is at the discretion of the investigators based on the condition of each patient.</description>
    <arm_group_label>Adjuvant Chemotherapy plus GM1</arm_group_label>
    <arm_group_label>Adjuvant Chemotherapy plus placebo</arm_group_label>
    <other_name>Oxalipaltin</other_name>
    <other_name>Leucovorin</other_name>
    <other_name>Calcium Folinate</other_name>
    <other_name>5-Fluorouracil</other_name>
    <other_name>Capecitabine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age: 18-75 years old, male or female&#xD;
&#xD;
          -  Histologically confirmed diagnosis of colorectal adenocarcinoma with a phase II or III&#xD;
             disease, within 2 months from radical resection, and intends to receive 6 months of&#xD;
             adjuvant chemotherapy with mFOLOFX6 or XELOX, without adjuvant radiation indications&#xD;
&#xD;
          -  No prior any level of peripheral nerve system disease&#xD;
&#xD;
          -  Patients have not received any other possible neurotoxic-reaction-causing drugs (such&#xD;
             as oxaliplatin, cisplatin and paclitaxel drugs etc)&#xD;
&#xD;
          -  With the capability to accurately record the occurrence and severity of neurotoxicity&#xD;
             by questionnaire&#xD;
&#xD;
          -  With normal functions of major organs&#xD;
&#xD;
          -  No contraindication to chemotherapy&#xD;
&#xD;
          -  Life expectancy ≥ 3 months&#xD;
&#xD;
          -  Patients have provided a signed Informed Consent Form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who received radical resection, but are expected not be able to complete 6&#xD;
             months of adjuvant chemotherapy&#xD;
&#xD;
          -  Patients who receive palliative chemotherapy&#xD;
&#xD;
          -  Patients who need adjuvant or palliative radiotherapy during chemotherapy&#xD;
&#xD;
          -  Be allergic to GM1&#xD;
&#xD;
          -  Hereditary abnormal metabolism of glucose and lipid&#xD;
&#xD;
          -  Doctors believe that patients are not suitable for receiving GM1 treatment&#xD;
&#xD;
          -  With confirmed history of neurological or psychiatric disorders, including epilepsy&#xD;
             and dementia&#xD;
&#xD;
          -  With concomitant diseases that will seriously harm the patients' safety or impact the&#xD;
             completion of the study&#xD;
&#xD;
          -  Patients (male or female) have fertility possibility but not willing or not to take&#xD;
             effective contraceptive measures&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yuhong Li, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>September 21, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 29, 2014</study_first_posted>
  <last_update_submitted>October 3, 2019</last_update_submitted>
  <last_update_submitted_qc>October 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Yuhong Li</investigator_full_name>
    <investigator_title>MD Ph D</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Neurotoxicity Syndromes</mesh_term>
    <mesh_term>Neutropenia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02251977
org study id: GOXL-18
nct id: NCT02251977
lead sponsor: 
has dmc: Yes
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: rates of grade 2 or more chronic cumulative neurotoxicity of both arms
time frame: 9 months
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
measure: rates of chronic cumulative neurotoxicity of both arms
time frame: 9 months
description: measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20
measure: time to grade 2 or more neurotoxicity of both arms
time frame: 9 months
measure: rates of dose reduction or withdrawal due to oxaliplatin induced neurotoxicity of both arms
time frame: 9 months
measure: rates of acute neurotoxicity of both arms
time frame: 6 months
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
measure: rates and grades of adverse reactions of both arms
time frame: 6 months
measure: rates of 3 year disease free survival of both arms
time frame: 3 years
measure: change degrees of the levels of nerve growth factor and other neurotrophic factors of both arms
time frame: 6 months
measure: genetic polymorphisms of oxaliplatin induced severe and cumulative neurotoxicity
time frame: 6 months
arm group label: Adjuvant Chemotherapy plus GM1
arm group type: Experimental
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.
arm group label: Adjuvant Chemotherapy plus placebo
arm group type: Placebo Comparator
description: 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).
intervention type: Drug
intervention name: GM1
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.
arm group label: Adjuvant Chemotherapy plus GM1
other name: monosialotetrahexosylganglioside
intervention type: Drug
intervention name: placebo
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.
arm group label: Adjuvant Chemotherapy plus placebo
intervention type: Drug
intervention name: mFOLFOX6 or XELOX
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.
arm group label: Adjuvant Chemotherapy plus GM1
arm group label: Adjuvant Chemotherapy plus placebo
other name: Oxalipaltin
other name: Leucovorin
other name: Calcium Folinate
other name: 5-Fluorouracil
other name: Capecitabine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Yuhong Li, MD
role: Principal Investigator
affiliation: Sun Yat-sen University
facility: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Yuhong Li
investigator title: MD Ph D
mesh term: Colorectal Neoplasms
mesh term: Neurotoxicity Syndromes
mesh term: Neutropenia
mesh term: Leucovorin
mesh term: Fluorouracil
mesh term: Capecitabine