The Use of Glutathione (GSH) for Prevention of Paclitaxel/Carboplatin (TAXOL/CBDCA) Induced Peripheral Neuropathy: A Phase III Randomized, Double-Blind Placebo Controlled Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 195
- 试验地点
- 388
- 主要终点
- Paclitaxel/Carboplatin (PC) Induced Peripheral Neuropathy as Assessed by EORTC QLQ-CIPN20 (European Organization for Research and Treatment of Cancer (EORTC), Quality of Life (QLQ), Chemotherapy Induced Peripheral Neuropathy 20 (CIPN20)).
研究概览
简要总结
This randomized phase III trial is studying glutathione to see how well it works in preventing peripheral neuropathy caused by paclitaxel and carboplatin in patients with ovarian cancer, fallopian tube cancer, and/or primary peritoneal cancer. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemoprotective drugs, such as glutathione, may help prevent peripheral neuropathy caused by paclitaxel and carboplatin. It is not yet known whether glutathione is more effective than a placebo in preventing peripheral neuropathy.
详细描述
PRIMARY OBJECTIVES:
I. To compare TAXOL (paclitaxel)/carboplatin (CBDCA) induced peripheral neuropathy as measured by European Organization for Research and Treatment of Cancer (EORTC)- Quality of Life (QOL)-chemotherapy induced peripheral neuropathy 20 (CIPN20) between glutathione (GSH) and placebo arms.
SECONDARY OBJECTIVES:
I. To compare the incidences of grade 2+ and grade 3+ TAXOL/CBDCA induced peripheral neuropathy measured by Common Terminology Criteria for Adverse Events (CTCAE) neuropathy scale between GSH and placebo arms.
II. To compare the time to onset of grade 2+ and grade 3+ TAXOL/CBDCA induced peripheral neuropathy between GSH and placebo arms, measured by CTCAE neuropathy scale.
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
- Triple (Participant, Care Provider, 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
- •Scheduled to undergo treatment with TAXOL at 150-200 mg/m2 and CBDCA at area under the curve (AUC) = 5-7 every 21 or 28 days for at least 12 weeks; alternatively, paclitaxel can be prescribed at 80 mg/m2 weekly for at least 12 weeks, with the same CBDCA dose of AUC = 5-7 every 21 days; additional chemotherapy agents are allowed (bevacizumab, etoposide, etc) per physician discretion, as long as they are not known to be neurotoxic; Note: patients ideally will begin GSH therapy prior to their first dose of this chemotherapy, but must begin GSH therapy prior to their second dose of chemotherapy
- •Ability to sign informed consent and understand the nature of a placebo-controlled trial
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Ability to complete English language questionnaire(s) by themselves or with assistance
- •Life expectancy >= 6 months
- •Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only, per clinician discretion
- •Willingness to provide blood specimens as required by the protocol
- •White blood cell (WBC) >= 3400
- •Absolute neutrophil count (ANC) >= 1500
- •Platelet (PLT) >= 100,000
- •Hemoglobin (HgB) > 10.0
- •Creatinine =< 1.5 x upper limit of normal (ULN)
排除标准
- •Pre-existing history of peripheral neuropathy > grade 1 (National Cancer Institute [NCI] CTCAE version [v] 4.0) due to any cause (e.g., chemotherapy, diabetes, alcohol, toxin, or heredity)
- •Other medical conditions, which in the opinion of the treating physician/allied health professional would make this protocol unreasonably hazardous for the patient
- •Any of the following:
- •Pregnant women
- •Nursing women
- •Women of childbearing potential who are unwilling to employ adequate contraception
- •Prior TAXOL and/or CBDCA chemotherapy treatment (other than the current treatment regimen)
- •Concurrent use of any agent being used specifically to prevent or treat neuropathy, including but not limited to the following:
- •Gabapentin
- •Glutamine powder or glutamine tablets
- •Vitamin B6 or E
研究组 & 干预措施
Arm I (glutathione, carboplatin)
Patients receive glutathione intravenously (IV) over 15 minutes, paclitaxel* IV over 1 or 3 hours depending on planned dose cycle length and carboplatin IV over 30 minutes.
干预措施: Carboplatin (Drug)
Arm I (glutathione, carboplatin)
Patients receive glutathione intravenously (IV) over 15 minutes, paclitaxel* IV over 1 or 3 hours depending on planned dose cycle length and carboplatin IV over 30 minutes.
干预措施: Glutathione (Drug)
Arm I (glutathione, carboplatin)
Patients receive glutathione intravenously (IV) over 15 minutes, paclitaxel* IV over 1 or 3 hours depending on planned dose cycle length and carboplatin IV over 30 minutes.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (glutathione, carboplatin)
Patients receive glutathione intravenously (IV) over 15 minutes, paclitaxel* IV over 1 or 3 hours depending on planned dose cycle length and carboplatin IV over 30 minutes.
干预措施: Paclitaxel (Drug)
Arm I (glutathione, carboplatin)
Patients receive glutathione intravenously (IV) over 15 minutes, paclitaxel* IV over 1 or 3 hours depending on planned dose cycle length and carboplatin IV over 30 minutes.
干预措施: Quality-of-Life Assessment (Other)
Arm II (placebo, paclitaxel)
Patients receive placebo IV over 15 minutes, paclitaxel* IV over 1 or 3 hours depending on planned dose cycle length and carboplatin IV over 30 minutes.
干预措施: Carboplatin (Drug)
Arm II (placebo, paclitaxel)
Patients receive placebo IV over 15 minutes, paclitaxel* IV over 1 or 3 hours depending on planned dose cycle length and carboplatin IV over 30 minutes.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (placebo, paclitaxel)
Patients receive placebo IV over 15 minutes, paclitaxel* IV over 1 or 3 hours depending on planned dose cycle length and carboplatin IV over 30 minutes.
干预措施: Paclitaxel (Drug)
Arm II (placebo, paclitaxel)
Patients receive placebo IV over 15 minutes, paclitaxel* IV over 1 or 3 hours depending on planned dose cycle length and carboplatin IV over 30 minutes.
干预措施: Placebo (Other)
Arm II (placebo, paclitaxel)
Patients receive placebo IV over 15 minutes, paclitaxel* IV over 1 or 3 hours depending on planned dose cycle length and carboplatin IV over 30 minutes.
干预措施: Quality-of-Life Assessment (Other)
结局指标
主要结局
Paclitaxel/Carboplatin (PC) Induced Peripheral Neuropathy as Assessed by EORTC QLQ-CIPN20 (European Organization for Research and Treatment of Cancer (EORTC), Quality of Life (QLQ), Chemotherapy Induced Peripheral Neuropathy 20 (CIPN20)).
时间窗: Every 28 day cycle, up to 6 cycles.
The CIPN sensory subscale will be calculated by standard scoring algorithm and converted to 0-100 scale (higher scores indicated less symptoms and better quality of life). Generalized linear models (repeated measures analysis of variance \[ANOVA\] if data are complete) will be used to compare the CIPN between Glutathione (GSH) and placebo arms.
次要结局
- Change in Patient Reported Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Ovarian (FACT-O) and Patient Daily-symptom Questionnaires Over Time.(Baseline to 1 year)
- Recurrence-free Survival (for Patients Without Clinical Evidence of Disease)(Up to 1 year)
- Paclitaxel Acute Pain Syndrome Incidence and Severity Between GSH and Placebo Arms(Up to 1 year)
- Percentage of Patients Delaying PC Chemotherapy Secondary to PN(Up to 1 year)
- Percentage of Patients Undergoing Dose Reductions Secondary to PCI PN(Up to 1 year)
- Percentage of Patients With Grade 2+ and Grade 3+ Paclitaxel/Carboplatin-induced (PCI) Peripheral Neuropathy (PN) According to the Common Terminology Criteria for Adverse Events (CTCAE) Neuropathy Scale(Up to 1 year)
- Times to Onset of CTCAE Grade 2+ PN(Up to 1 year)
- Times to Onset of CTCAE Grade 3+ PN(Up to 5 years from registration)