The Effect of Monosialotetrahexosyl Ganglioside (GM1) in Prevention of Taxanes Induced Neurotoxicity in Breast Cancer Patients Who Received Taxanes-based Adjuvant Chemotherapy: A Multi-center, Randomized, Placebo-controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 206
- 试验地点
- 1
- 主要终点
- the Functional Assessment of Cancer Treatment Neurotoxicity (FACT-Ntx) subscale between groups at 2 weeks after the 4-cycle chemotherapy
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •There are any toxicity events of peripheral nervous system before enrollment, including: FACT-Ntx subscale score < 44;≥ Grade 1 peripheral toxicity according to CTCAE Version 4.0 rating scale;≥ Grade 1 peripheral toxicity according to ENS rating scale;All other pathological symptoms or diseases might affect the evaluation of adverse neurotoxic effects
- •Patients having received other drug treatments might cause similar adverse neurotoxic effects within 4 weeks prior to the treatment of this protocol, or receive concurrent neurotoxic drugs. Including: Taxanes or analogues; Vinca alkaloids or analogues; Platinums or analogues; Cytarabine, thalidomide, bortezomib, or procarbazine; Other drugs or treatments might cause peripheral neurotoxicity
- •Patients in poor general conditions, with KPS (Karnofsky performance status) scores < 80;
- •Pregnant or lactating women；
- •Patients (female) having the possibility of fertility but unwilling or not taking effective contraceptive measures
- •Patients also having other neurological abnormalities who cannot accurately record the occurrence and severity of neurotoxicity;
- •Patients known allergy to trial drugs or excipient compositions of these products;
- •Patients with inherited glucose and lipid metabolism abnormalities (gangliosidosis such as amaurotic family idiocy and retinopathy);
- •Patients not suitable for treatment of ganglioside;
- •Active infection (depending on the judgment of investigators);
- •Patients with serious concurrent diseases might harmful to safety and interfere the scheduled treatment or concomitant diseases might affect the completion of the study, depending on the judgment of investigators.
- •Patients with a history of definite neurological or dysphrenia, including epilepsy or dementia.
研究组 & 干预措施
Ganglioside-monosialic acid arm
Patients will receive treatment of adjuvant chemotherapy. Ganglioside-monosialic acid(GM1, 80mg per day) will be given at 1 day before the start of chemotherapy for three days (Day -1, 1 and 2).
Chemotherapy regimens:
Epirubicin (90 mg/m2) combined with cyclophosphamide (600 mg/m2) followed by paclitaxel (175 mg/m2 *4 cycles) after four courses of chemotherapy; Epirubicin (90 mg/m2) combined with cyclophosphamide (600 mg/m2) followed by docetaxel (75 mg/m2 *4 cycles) after four course of chemotherapy; Docetaxel (75 mg/m2 q21d) combined with cyclophosphamide (600 mg/m2) for four courses.
The first day (D1) of each cycle is treated with taxane-based chemotherapy. 14-21 days are usually as one cycle. The methods of pretreatment and hydration shall be decided by the physicians.
干预措施: Ganglioside-monosialic acid (Drug)
placebo arm
Patients will receive treatment of adjuvant chemotherapy. Placebo will be given at 1 day before the start of chemotherapy for three days (Day -1, 1 and 2).
Chemotherapy regimens:
Epirubicin (90 mg/m2) combined with cyclophosphamide (600 mg/m2) followed by paclitaxel (175 mg/m2 *4 cycles) after four courses of chemotherapy; Epirubicin (90 mg/m2) combined with cyclophosphamide (600 mg/m2) followed by docetaxel (75 mg/m2 *4 cycles) after four course of chemotherapy; Docetaxel (75 mg/m2 q21d) combined with cyclophosphamide (600 mg/m2) for four courses.
The first day (D1) of each cycle is treated with taxane-based chemotherapy. 14-21 days are usually as one cycle. The methods of pretreatment and hydration shall be decided by the physicians.
干预措施: placebo (Drug)
结局指标
主要结局
the Functional Assessment of Cancer Treatment Neurotoxicity (FACT-Ntx) subscale between groups at 2 weeks after the 4-cycle chemotherapy
时间窗: Day 1 of Week 1 to 1 year after the last course of chemotherapy
The primary endpoint was assessed using the Functional Assessment of Cancer Treatment, Gynecologic Oncology Group Neurotoxicity (FACT -Ntx) subscale at 2 weeks after completion of 4-cycles of taxane-based chemotherapy. FACT-Ntx subscales contains 11 items including numbness, tingling, and discomfort in the hands or feet; difficulty hearing or tinnitus; joint pain or muscle cramps; weakness or fatigue; or trouble walking, buttoning buttons, or feeling small shapes when placed in the hand; feeling pain or hard to breath when exposed to low temperature. Each Items is scored from 0 to 4 with a total score of 44; higher scores indicate better performance. A 5-point difference in the FACT-Ntx subscale scores between groups is considered clinically meaningful. The FACT-Ntx subscales assessments 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.
次要结局
- neurotoxicity evaluated by NCI-CTCAE version 4.0 grading scale(1 monthDay 1 of Week 1 to 1 year after the last course of chemotherapy)
- neurotoxicity evaluated by the Eastern Cooperative Oncology Group neuropathy scale (ENS) subscales of sensory neuropathy, motor neurotoxicity, and neurogenic constipation.(Day 1 of Week 1 to 1 year after the last course of chemotherapy)
研究者
Zhong-yu Yuan
chief physician
Sun Yat-sen University