Effect of GM1 in Prevention of Taxanes Induced Neurotoxicity in Operable Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms; Neurotoxicity Syndromes
Study type: Interventional
Phase: Phase 3

Summary: 
      Background: Taxane plays a key role in the treatment of breast cancer and taxane-induced
      peripheral neuropathy (TIPN) is a dose-limiting adverse effect leading to treatment
      discontinuation. Ganglioside-monosialic acid (GM1) functions as a neuroprotective factor.
      However, the effects of GM1 on TIPN in breast cancer patients remains unknown.

      Purpose: This randomized phase III trial is designed to evaluate the potential effects of GM1
      for preventing TIPN in breast cancer patients.
    

Detailed description: 
      Introduction： Taxanes is a key agent in the treatment of breast cancer. However, peripheral
      neuropathy markedly limits the use of taxanes. Unfortunately, current studies have neither
      revealed a clear mechanism nor established an effective treatment for Taxane-induced
      peripheral neuropathy (TIPN). Monosialotetrahexosyl ganglioside (GM1) functions as a
      neuroprotective factor. This multi-center, randomized, placebo-controlled trial was performed
      to assess the efficacy of GM1 fo preventing taxanes induced neurotoxicity in operable breast
      cancer patients who received taxanes-based adjuvant chemotherapy.

      OBJECTIVES:

      Primary Objective:

      To evaluate the efficacy of gangliosides in the prevention of neurotoxicity in breast cancer
      patients treated with taxane-based chemotherapy. That is, to compare the differences in the
      scores of Functional Assessment of Cancer Treatment Neurotoxicity (FACT-Ntx) between the
      patients treated by GM1(the treatment group) and the placebo (the control group) at 2 weeks
      after completion of 4-cycles of taxane-based chemotherapy.

      Secondary

        -  To compare the differences in the scores of Eastern Cooperative Oncology Group
           neuropathy scale between the patients treated by gangliosides (the experimental group)
           and the placebo (the control group);

        -  Tocompare the incidence of neurotoxic adverse events caused by taxane-based
           chemotherapy. That is, the difference between the patients of chemotherapy treated by
           gangliosides (the experimental group) and the placebo (the control group) in terms of
           the incidence of neurotoxicity (graded according to the NCI-CTCAE version 4.0 grading
           scale);

        -  Assess the safety and tolerance of the two treatment groups (ganglioside and placebo
           groups).

      OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients with
      early-stage breast cancer planning to receive taxane-based adjuvant chemotherapy were
      randomly assigned to receive GM1 (80 mg, Day -1 to Day 2) or placebo treatment.

      Treatment group: Monosialotetrahexosylganglioside sodium is added into 250 mL of 0.9% sodium
      chloride injection, which is given once a day via intravenous drip infusion for 3 days. The
      first dose is given at 1 day before the start of the chemotherapy. At the same time, the
      patients are treated with a taxane-based chemotherapy selected by the investigators.

      Placebo group: Placebo is added into 250 mL of 0.9% sodium chloride injection, which is given
      once a day via intravenous drip infusion for 3 days. The first dose is given at 1 day before
      the start of the chemotherapy. At the same time, the patients are treated with a taxane-based
      chemotherapy selected by the investigators.

      The screening and baseline peripheral neurotoxicity assessment was performed 1 day before the
      start of the first course of taxane-containing chemotherapy.

      The subjects will be treated by the study drugs according to the schedule until the
      completion of established taxane-based adjuvant chemotherapy, the onset of unacceptable
      toxicity, or when the patient withdraw from the study voluntarily.

      Endpoint assessments including FACT-Ntx subscale, CTCAE version 4.0 grading scale and ENS
      subscales were performed at 2 weeks after each course of chemotherapy. Additional long-term
      assessments were performed at 3 months, 6 months and 1 year after the end of chemotherapy.
      The follow-up will be carried out until 2 years after the enrollment time of the last
      patient.
    

Intervention name(s): Ganglioside-monosialic acid; placebo
Intervention type(s): Drug; Drug
Intervention description(s): Ganglioside-monosialic sodium is added into to 250 ml of 0.9% sodium chloride injection, which is given once a day via intravenous drip infusion for 3 days. The first dose is given at 1 day before the start of the chemotherapy.(day -1, day 1 and day2). The dosages of GM1 are 80mg per day.; Placebo is added into to 250 ml of 0.9% sodium chloride injection, which is given once a day via intravenous drip infusion for 3 days. The first dose is given at 1 day before the start of the chemotherapy.(day -1, day 1 and day2).
Other intervention name(s): GM1
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention