Phase I Trial of GLIADEL and O(6)-Benzylguanine in Pediatric Patients With Recurrent Malignant Gliomas
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 18
- 主要终点
- Biologically effective dose of O(6)-benzylguanine administered continuously in pediatric patients with recurrent malignant glioma
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemotherapy placed into the surrounding tissue after surgery to remove the tumor may kill any remaining tumor cells. O(6)-benzylguanine may increase the effectiveness of carmustine by making tumor cells more sensitive to the drug.
PURPOSE: Phase I trial to study the safety of combining O(6)-benzylguanine with carmustine implants in treating children who have recurrent malignant glioma.
详细描述
OBJECTIVES:
- Determine the dose of O(6)-benzylguanine that reliably inhibits alkylguanine-DNA alkyltransferase activity in pediatric patients with recurrent malignant glioma.
- Describe the toxic effects of O(6)-benzylguanine with carmustine implant (Gliadel) in these patients.
- Investigate antitumor response in patients treated with this regimen.
- Characterize the pharmacokinetics of O(6)-benzylguanine when administered continuously over a 9-day period.
OUTLINE: This is a multicenter, dose-escalation study of O(6)-benzylguanine.
Patients receive O(6)-benzylguanine (O6-BG) IV over 1 hour immediately followed by O6-BG IV continuously for 9 days. Two days after initiation of continuous infusion of O6-BG, patients undergo maximal tumor debulking. At the time of surgery, patients receive up to 8 polifeprosan 20 wafers with carmustine (Gliadel) implanted into the resection cavity.
Cohorts of up to 14 patients receive escalating doses of continuous infusion O6-BG until the optimally biologically effective dose (BED) is determined. The BED is defined as the dose at which at least 11 of 14 patients meet the target of complete suppression of alkylguanine-DNA alkyltransferase levels.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
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 progressive supratentorial anaplastic astrocytoma or glioblastoma multiforme
- •No multifocal disease or leptomeningeal dissemination of tumor
- •No evidence of tumor crossing midline
- •Limited intraventricular involvement
- •Measurable unilateral mass at least 10 mm by contrast-enhanced MRI
- •Received prior involved-field radiotherapy as a component of prior therapy
- •Amenable to and in need of significant debulking
- •PATIENT CHARACTERISTICS:
- •Performance status
- •Karnofsky 60-100% OR
- •Lansky 60-100%
- •Life expectancy
- •More than 8 weeks
- •Hematopoietic
- •Absolute neutrophil count greater than 1,000/mm3*
- •Platelet count greater than 100,000/mm3*
- •Hemoglobin greater than 8 g/dL (transfusions allowed) NOTE: * Transfusion independent
- •Bilirubin no greater than 1.5 times normal
- •AST and ALT less than 3 times normal
- •Albumin at least 2 g/dL
- •No overt hepatic disease
- •Creatinine clearance no greater than 1.5 times normal OR
- •Glomerular filtration rate greater than 70 mL/min
- •No overt renal disease
- •Cardiovascular
- •No overt cardiac disease
- •No overt pulmonary disease
- •Neurological deficits must be stable for at least the past week
- •No uncontrolled infection
- •No known hypersensitivity to nitrosoureas or polyethylene glycol
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •At least 6 months since prior bone marrow transplantation
- •More than 2 weeks since prior colony-stimulating growth factors (e.g., filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa)
- •Chemotherapy
- •No more than 2 prior cytotoxic chemotherapy regimens
- •No more than 3 prior chemotherapy regimens total
- •More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered
- •Prior systemic carmustine (or other nitrosourea) allowed provided patient did not experience non-hematopoietic grade III/IV toxicity
- •Endocrine therapy
- •Concurrent dexamethasone allowed if on a stable dose for at least the past week
- •Radiotherapy
- •See Disease Characteristics
- •At least 3 months since prior radiotherapy
- •No prior craniospinal irradiation for metastatic disease
- •See Disease Characteristics
- 另有 3 项未显示
排除标准
- 未提供
结局指标
主要结局
Biologically effective dose of O(6)-benzylguanine administered continuously in pediatric patients with recurrent malignant glioma
Toxicities associated with the administration of O(6)-benzylguanine and carmustine implants.
次要结局
- Tumor response