Phase I/II Trial Of Intracerebral IL13-PE38QQR Infusions In Pediatric Patients With Recurrent Malignant Glioma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 主要终点
- Toxicities from the start of infusion through the dose limiting toxicity observation period(Phase I)
研究概览
简要总结
RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of immunotoxin therapy and to see how well it works in treating children undergoing surgery for recurrent or progressive malignant glioma.
详细描述
OBJECTIVES:
Primary
- Determine the toxicity of peritumoral IL13-PE38QQR after surgical resection in pediatric patients with recurrent malignant gliomas. (Phase I)
- Determine the maximum tolerated flow rate and maximum tolerated infusion concentration (MTiC) of this drug in these patients. (Phase I)
- Estimate the rate of survival after initial progression in patients treated at the maximum safe flow rate and MTiC with this drug. (Phase II)
Secondary
- Describe the overall safety and tolerability of this regimen in these patients from the start of infusion through disease progression or initiation of alternative treatment.
- Determine the IL13 receptor α2 chain expression status and distribution in pediatric recurrent or progressive malignant gliomas
- Estimate the progression-free survival of patients treated with this drug. (Phase II)
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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed grade 3 or 4 supratentorial malignant glioma by prior surgery or biopsy
- •Anaplastic astrocytoma
- •Glioblastoma multiforme
- •Malignant mixed oligoastrocytoma
- •Recurrent or progressive disease by radiology
- •In first progression or recurrence (for patients in the phase II portion of the study only)
- •Must have 1 solid primary lesion with a solid component measuring at least 1 cm in diameter
- •Must have received external beam radiotherapy with tumor dose of at least 48 Gy
- •Planning to undergo gross total resection of the tumor to remove all contrast-enhancing components of the tumor
- •No multifocal tumor not amenable to gross tumor resection
- •No contrast-enhancing tumor component crossing the midline
- •No subependymal or leptomeningeal tumor dissemination
- •No clinically significant increased intracranial pressure (e.g., impending herniation)
- •No spinal cord compression
- •No requirement for immediate palliative treatment
- •PATIENT CHARACTERISTICS:
- •Performance status
- •Karnofsky 60-100% (over 16 years of age)
- •Lansky 60-100 (16 years of age and under)
- •Life expectancy
- •Not specified
- •Hematopoietic
- •Absolute neutrophil count at least 1,500/mm^3
- •Hemoglobin at least 10 g/dL*
- •Platelet count at least 100,000/mm^3* NOTE: *Transfusion independent
- •PT and PTT normal
- •Creatinine normal for age
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No uncontrolled seizures
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •At least 8 weeks since prior hematopoietic stem cell transplantation
- •Chemotherapy
- •No prior intracerebral chemotherapy for malignant glioma (except polifeprosan 20 with carmustine implant)
- •At least 6 months since prior polifeprosan 20 with carmustine implant
- •At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas)
- •At least 2 weeks since prior vincristine or noncytotoxic chemotherapy
- •No concurrent chemotherapy
- •Endocrine therapy
- •Concurrent steroids allowed
- •Radiotherapy
- •See Disease Characteristics
- •At least 8 weeks since prior radiotherapy
- •No prior focal radiotherapy for malignant glioma (e.g., single-fraction stereotaxic radiotherapy or brachytherapy)
- •Prior stereotactic radiosurgery boost as part of the initial fractionated external beam radiotherapy regimen allowed
- •See Disease Characteristics
- •Recovered from prior therapy
- 另有 9 项未显示
排除标准
- 未提供
结局指标
主要结局
Toxicities from the start of infusion through the dose limiting toxicity observation period(Phase I)
时间窗: Start of IL13-PE38QQR infusion to Day 35 or Day 75
Toxicities reported are those occurring from the start of the IL13 infusion after catheter placement to Day 35 (30 days after the end of the infusion) if there are no or mild MRI changes on Day 35 around the catheter tract or tip. If the MRI change on Day 35 indicates moderate or extensive changes around the catheter tract or tip then the toxicities reported are those occurring from the start of the IL13 infusion to Day 75 (70 days after the end of the infusion).
Maximum safe flow rate (Phase I)
时间窗: Start of IL13-PE38QQR infusion to Day 35 or Day 70
Two total flow rates of IL13-PE38QQR, 500 uL/hr and 750 uL/hr, will be studied based on a traditional phase I design. Dose-limiting toxicities occurring during the dose-finding period will determine the maximum safe flow rate. The dose-finding period is the start of the IL13 infusion after catheter placement to Day 35 if there are none or mild MRI changes around the catheter tract or tip on Day 35. If there are moderate or extensive MRI changes around the catheter tract or tip on Day 35 then the dose-finding period is from the start of the IL13 infusion to Day 75.
Maximum tolerated infusion concentration (Phase I)
时间窗: Start of IL13-PE38QQR infusion to Day 35 or Day 70
Two infusion concentrations of IL13-PE38QQR, .25 ug/mL and .50 ug/mL, will be studied based on a traditional phase I design. Dose-limiting toxicities occurring during the dose-finding period will determine the maximum tolerated infusion concentration. The dose-finding period is the start of the IL13 infusion after catheter placement to Day 35 if there are none or mild MRI changes around the catheter tract or tip on Day 35. If there are moderate or extensive MRI changes around the catheter tract or tip on Day 35 then the dose-finding period is from the start of the IL13 infusion to Day 75.
Survival post initial recurrence or progression at the maximum safe total flow rate and maximum tolerated infusion concentration (Phase II)
时间窗: Initial progression to date of death from any cause
次要结局
- Progression-free survival (Phase II)(Initial progression to second progression)
- IL13receptor α2 chain expression status and distribution(Pre-treatment)
- Overall safety(Start of IL13-PE38QQR infusion to disease progression or alternative treatment)
- Tolerability(Start of IL13-PE38QQR infusion to disease progression or alternative treatment)