A Phase II Study of Concurrent Radiation and Temozolomide Followed By Temozolomide and CCNU in the Treatment of Children With High-Grade Glioma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 118
- 试验地点
- 1
- 主要终点
- One Year Overall Survival
研究概览
简要总结
This phase II trial is studying how well giving radiation therapy together with temozolomide and lomustine works in treating young patients with newly diagnosed gliomas. Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide and lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with temozolomide and lomustine after surgery may kill any remaining tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. Compare event-free survival of pediatric patients with newly diagnosed high-grade gliomas treated with adjuvant radiotherapy and temozolomide followed by temozolomide and lomustine with historical controls.
II. Determine the toxicity of this regimen in these patients. III. Correlate MGMT and p53 expression in tumor tissue with outcome in patients treated with this regimen.
IV. Correlate polymorphisms in GSTP1, GSTM1 and GSTT1 genes and GSTP1 protein expression in tumors with survival in patients treated with this regimen.
OUTLINE: This is a pilot, multicenter study.
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
- 3 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed, newly diagnosed high-grade glioma of 1 of the following histologies:
- •Anaplastic astrocytoma
- •Glioblastoma multiforme
- •Gliosarcoma
- •Primary spinal cord malignant gliomas allowed
- •No primary brainstem tumors
- •Has undergone surgical resection or biopsy of the tumor within the past 31 days
- •Pre-operative and post-operative brain MRI with and without gadolinium-contrast OR pre-operative and post-operative spine MRI for spinal cord primaries
- •Post-operative MRI not required for patients who undergo biopsy only
- •No evidence of neuraxis dissemination
- •Spine MRI and cerebrospinal fluid cytology required only if clinically indicated
- •Performance status - Karnofsky 50-100% (for patients > 16 years of age)
- •Performance status - Lansky 50-100% (for patients ≤ 16 years of age)
- •At least 8 weeks
- •Absolute neutrophil count ≥ 1,000/mm^3
- •Platelet count ≥ 100,000/mm^3 (transfusion independent)
- •Hemoglobin ≥ 8 g/dL (transfusions allowed)
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •ALT ≤ 2.5 times ULN
- •Albumin ≥ 2 g/dL
- •Creatinine ≤ 1.5 times ULN
- •Creatinine clearance or radioisotope glomerular filtration rate ≥ lower limit of normal
- •No evidence of dyspnea at rest
- •No exercise intolerance
- •Pulse oximetry ≥ 94% (if determination is clinically indicated)
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 2 months after study participation
- •Able to swallow oral medication
- •Seizures allowed provided they are well controlled with anticonvulsants
- •No hypersensitivity to temozolomide
- •No prior biologic agents
- •No prior chemotherapy
- •Prior corticosteroids allowed
- •No concurrent corticosteroids as an antiemetic
- •Concurrent corticosteroids allowed only for treatment of increased intracranial pressure
- •No concurrent radiotherapy using cobalt-60
- •See Disease Characteristics
- •No other prior treatment
- •No concurrent phenobarbital or cimetidine
- •No concurrent co-trimoxazole for Pneumocystis carinii pneumonia prophylaxis during study chemoradiotherapy
排除标准
- 未提供
研究组 & 干预措施
Treatment (lomustine, temozolomide, radiation therapy)
Patients receive oral temozolomide once daily on days 1-42. Patients also undergo concurrent radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33 and 36-40. Patients who did not undergo prior gross total resection also undergo boost radiotherapy once daily on days 43-47. Four weeks after completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5 and oral lomustine on day 1. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (lomustine, temozolomide, radiation therapy)
Patients receive oral temozolomide once daily on days 1-42. Patients also undergo concurrent radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33 and 36-40. Patients who did not undergo prior gross total resection also undergo boost radiotherapy once daily on days 43-47. Four weeks after completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5 and oral lomustine on day 1. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Lomustine (Drug)
Treatment (lomustine, temozolomide, radiation therapy)
Patients receive oral temozolomide once daily on days 1-42. Patients also undergo concurrent radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33 and 36-40. Patients who did not undergo prior gross total resection also undergo boost radiotherapy once daily on days 43-47. Four weeks after completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5 and oral lomustine on day 1. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Radiation Therapy (Radiation)
Treatment (lomustine, temozolomide, radiation therapy)
Patients receive oral temozolomide once daily on days 1-42. Patients also undergo concurrent radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33 and 36-40. Patients who did not undergo prior gross total resection also undergo boost radiotherapy once daily on days 43-47. Four weeks after completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5 and oral lomustine on day 1. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Temozolomide (Drug)
结局指标
主要结局
One Year Overall Survival
时间窗: One year
Estimated one year survival using the Kaplan-Meier methodology.
Occurrence of Death Attributable to Complications of Protocol Therapy
时间窗: While receiving protocol therapy (up to 301 days excluding delays) or within 30 days of Termination of Protocol Therapy
Number of deaths due to complications of protocol therapy.
次要结局
未报告次要终点