An Early Phase and Phase II Clinical Trial to Evaluate Ganglioside-Monosialic Acid (GM1) for Preventing Paclitaxel-Associated Neuropathy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 7
- 试验地点
- 33
- 主要终点
- Maximum Tolerated Dose (Early phase)
研究概览
简要总结
This phase II trial tests the safety, side effects, and best dose of monosialotetrahexosylganglioside (GM1) and whether it works in reducing or preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) who are receiving treatment with paclitaxel. Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Exposure to chemotherapy drugs like paclitaxel may cause a side effect called CIPN, which is a condition of weakness, numbness, and pain from nerve damage (usually in the hands and feet). GM1 is a part of the body's natural system that insulates nerves and helps to protect nerves from damage. Giving GM1 may help reduce or prevent CIPN in breast cancer patients receiving treatment with paclitaxel.
详细描述
PRIMARY OBJECTIVES:
I. To obtain data to further support the safety of increasing monosialotetrahexosylganglioside (GM1) doses when given on day 1, concomitantly with paclitaxel. (Early phase) II. To evaluate the preliminary efficacy of GM1 compared with placebo at preventing paclitaxel-induced peripheral neuropathy sensory symptoms as measured by the six individual Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) questions that quantify numbness (N), tingling (T), and pain in the fingers/hands and toes/feet. (Phase II)
SECONDARY OBJECTIVES:
I. To obtain additional data to support the safety of GM1 in the treated population. (Phase II) II. To obtain data to support that GM1 looks promising for preventing/decreasing acute paclitaxel pain syndrome as measured by the Acute Pain Syndrome Questionnaire. (Phase II)
EXPLORATORY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documentation of disease: Histologic diagnosis of metastatic breast cancer in women or men
- •Prior treatment- No previous exposure to GM1
- •Planned administration of paclitaxel, either given weekly, or weekly 3 weeks on/1 week off, to patients with metastatic cancer at a dose of 80 mg/m^2
- •No planned treatment with concurrent immunotherapy
- •Score of 1 (none) and/or 2 (a little) on the six individual European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (QLQ)- chemotherapy-induced peripheral neuropathy (CIPN)20 questions that quantify numbness (N), tingling (T), and pain in the fingers/hands and toes/feet (Items #31-36)
- •No diagnosis of fibromyalgia
- •No history of significant respiratory tract infection and/or infectious diarrhea within 14 days before registration
- •No history of stroke or cerebrovascular accident in the past 6 months prior to registration
- •No history of diagnosed neurologic or psychiatric disorders, including epilepsy or dementia
- •For women of childbearing potential, not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
- •Therefore, for women of childbearing potential, a negative pregnancy test done =< 7 days prior to registration is required. Of note, a female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
- •Ability to complete questionnaires by themselves or with assistance
- •In order to complete the mandatory patient-completed measures, participants must be able to speak and/or read English and/or Spanish
- •Persons with impaired decision making such that they cannot understand the benefits or risks of trial participation, per the judgement of the consenting clinician, will not be eligible
- •Age >= 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Absolute neutrophil count (ANC) >= 1,000/mm^3
- •Platelet count >= 100,000/mm^3
- •Creatinine =< 1.5 x upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
- •Total bilirubin =< 1.5 x ULN
- •No planned use of duloxetine
- •No planned use of cryotherapy, compression therapy, or cryocompression therapy at study entry
排除标准
- 未提供
研究组 & 干预措施
Arm I (paclitaxel, GM1)
Patients receive GM1 IV 1 hour prior to paclitaxel administration and paclitaxel IV weekly for 12 weeks or 3 weeks on/1 week off for 12 doses.
干预措施: Questionnaire Administration (Other)
Arm II (paclitaxel, placebo)
Patients receive placebo IV 1 hour prior to paclitaxel administration and paclitaxel IV weekly for 12 weeks or 3 weeks on/1 week off for 12 doses.
干预措施: Paclitaxel (Drug)
Arm II (paclitaxel, placebo)
Patients receive placebo IV 1 hour prior to paclitaxel administration and paclitaxel IV weekly for 12 weeks or 3 weeks on/1 week off for 12 doses.
干预措施: Quality-of-life assessment (Other)
Arm II (paclitaxel, placebo)
Patients receive placebo IV 1 hour prior to paclitaxel administration and paclitaxel IV weekly for 12 weeks or 3 weeks on/1 week off for 12 doses.
干预措施: Placebo Administration (Drug)
Arm I (paclitaxel, GM1)
Patients receive GM1 IV 1 hour prior to paclitaxel administration and paclitaxel IV weekly for 12 weeks or 3 weeks on/1 week off for 12 doses.
干预措施: Quality-of-life assessment (Other)
Arm II (paclitaxel, placebo)
Patients receive placebo IV 1 hour prior to paclitaxel administration and paclitaxel IV weekly for 12 weeks or 3 weeks on/1 week off for 12 doses.
干预措施: Questionnaire Administration (Other)
Arm I (paclitaxel, GM1)
Patients receive GM1 IV 1 hour prior to paclitaxel administration and paclitaxel IV weekly for 12 weeks or 3 weeks on/1 week off for 12 doses.
干预措施: Monosialotetrahexosylganglioside (Drug)
Arm I (paclitaxel, GM1)
Patients receive GM1 IV 1 hour prior to paclitaxel administration and paclitaxel IV weekly for 12 weeks or 3 weeks on/1 week off for 12 doses.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Maximum Tolerated Dose (Early phase)
时间窗: 6-7 months
Defined as the highest dose level that induces dose-limiting toxicity in less than one-third of patients (less than 1 out of 3 or less than 2 out of a maximum of 6 new patients).The constellation of adverse events as scored using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, version (v) 5.0 (CTCAE v5.0) will be summarized by reporting the number and percentage of patients. Specifically, the number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized. The grade 3+ adverse events will also be described and summarized in a similar fashion. Further, all adverse events will be listed by system organ class and preferred term.
Composite response (Phase II)
时间窗: Up to one year
Reflects sensory paclitaxel-induced peripheral neuropathy symptom severity and onset. Measured using 6 individual Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) questions that quantify numbness (N), tingling (T) and pain in the fingers/hands and toes/feet. Will calculate the highest (worst) N, T, and pain sensory score obtained anytime during paclitaxel exposure. Response is defined as a patient reporting a highest score of =\< 2 without discontinuing the study due to sensory paclitaxel-induced peripheral neuropathy. Chi-squared test will be used. Will report the proportion of patients achieving a composite response in each arm as well as the difference in proportions along with the 90% confidence interval. Will report the estimated odds ratio (monosialotetrahexosylganglioside \[GM1\]/placebo) and the corresponding 90% confidence interval for the true, but unknown odds ratio. Multiple logistic regression will be used to estimate the intervention
次要结局
- Percentage of patients who received full planned dose of paclitaxel(up to 1 year)
- • Serially measured patient-reported outcome that best describes the patients' aches/pains at its worst in the last 24 hours(In the preceding 24 hours)
- • Sensory subscale of the European Organization of Research and Treatment of Cancer (EORTC) QLQ-CIPN20(Up to 1 year)
- Serially measured patient-reported outcome that best describes the patients' aches/pains at its least in the last 24 hours(in the preceding 24 hours)
- • Serially measured patient-reported outcome that best describes the patients' aches/pains on the average in the last 24 hours(in the preceding 24 hours)
- Rate of grade 3+ Adverse Events(Up to 1 year)