Phase I/II Trial of Oxaliplatin as Neoadjuvant Treatment in Adults With Newly Diagnosed Glioblastoma Multiforme
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 59
- 试验地点
- 1
- 主要终点
- Maximum-tolerated dose (MTD) defined as the dose level at which 2 out of 6 or the dose level below that at which >= 2 of 3 or > 2 of 6 patients experience dose-limiting toxicity (DLT) assessed by Common Toxicity Criteria (CTC) version 2.0 (Phase I)
研究概览
简要总结
This phase I/II trial is studying the side effects and best dose of oxaliplatin in treating patients with newly diagnosed glioblastoma multiforme. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing
详细描述
OBJECTIVES:
I. Determine the maximum tolerated dose of oxaliplatin in patients with newly diagnosed glioblastoma multiforme who are receiving or not receiving anticonvulsants known to be metabolized by P450.
II. Determine the dose-limiting toxicity and safety profile of this drug in this patient population.
III. Assess the pharmacokinetics of this drug on this schedule and determine the effects of P450-inducing anticonvulsants on the pharmacokinetics in these patients.
IV. Determine the radiographic response rate in patients treated with this drug.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Histologically confirmed supratentorial grade IV astrocytoma
- •Glioblastoma multiforme
- •Subtotal resection or biopsy with measurable and contrast-enhancing disease on the postoperative, pretreatment MRI/CT scan
- •Performance status - Karnofsky 60-100%
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Hemoglobin at least 9.0 g/dL
- •Bilirubin normal
- •Creatinine normal
- •Creatinine clearance at least 60 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No serious concurrent infection or medical illness that would jeopardize ability to receive protocol chemotherapy with reasonable safety
- •No other prior malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer
- •No grade 2 or greater pre-existing sensory neuropathy
- •No history of allergy to platinum compounds or to antiemetics appropriate for administration in conjunction with protocol chemotherapy
- •Mini mental score at least 15
- •No prior immunotherapy for glioblastoma multiforme
- •No prior biologic therapy for glioblastoma multiforme, including:
- •Immunotoxins
- •Immunoconjugates
- •Antiangiogenesis compounds
- •Antisense
- •Peptide receptor antagonists
- •Interferons
- •Interleukins
- •Tumor infiltrating lymphocytes
- •Lymphokine activated killer cells
- •Gene therapy
- •No concurrent filgrastim (G-CSF)
- •No prior chemotherapy for glioblastoma multiforme
- •No prior hormonal therapy for glioblastoma multiforme
- •Prior glucocorticoid therapy for glioblastoma multiforme allowed
- •Must be maintained on a stable (lowest required dose) corticosteroid regimen for at least 5 days before and during study
- •No concurrent dexamethasone as an antiemetic
- •No prior radiotherapy for glioblastoma multiforme
- •Recovered from immediate postoperative period
- •At least 10 days since prior anticonvulsant drug that induces hepatic metabolic enzymes
- •No other concurrent investigational agents
排除标准
- 未提供
研究组 & 干预措施
Treatment (oxaliplatin)
Patients receive oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days for a maximum of 6 courses in the absence of unacceptable toxicity or disease progression.
干预措施: oxaliplatin (Drug)
Treatment (oxaliplatin)
Patients receive oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days for a maximum of 6 courses in the absence of unacceptable toxicity or disease progression.
干预措施: pharmacological study (Other)
结局指标
主要结局
Maximum-tolerated dose (MTD) defined as the dose level at which 2 out of 6 or the dose level below that at which >= 2 of 3 or > 2 of 6 patients experience dose-limiting toxicity (DLT) assessed by Common Toxicity Criteria (CTC) version 2.0 (Phase I)
时间窗: 14 days
DLT is defined as grade 3 or 4 nonhematological toxicities or hematological toxicities as assessed by CTC version 2.0 (Phase I)
时间窗: 14 days
Pharmacokinetics of oxaliplatin (Phase I)
时间窗: At baseline, at immediately post infusion, at 2, 4, 22, and 24 hours (of course 1)
次要结局
- Response rate (Phase II)(Up to 7 years)
- Duration of survival (Phase II)(Up to 7 years)
- Frequency of toxicity as assessed by CTC version 2.0 (Phase II)(Up to 7 years after completion of study treatment)