Phase I Trial of Temozolomide and O6-Benzylguanine in Pediatric Patients With Recurrent Brain Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- MTD of temozolomide
研究概览
简要总结
Phase I trial to study the safety of combining O6-benzylguanine with temozolomide in treating children who have recurrent or refractory brain tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. O6-benzylguanine may increase the effectiveness of temozolomide by making tumor cells more sensitive to the drug.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose of temozolomide (Temodar) when administered with O6-benzylguanine (O6-BG) with and without G-CSF support to pediatric patients with refractory brain tumors stratified by previous radiotherapy.
SECONDARY OBJECTIVES:
I. To characterize the pharmacokinetics of temozolomide and O6-BG when used in combination.
II. To characterize toxicities associated with the combination of O6-BG and temozolomide with and without G-CSF support.
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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Recurrent or refractory pediatric brain tumors; a histopathologic diagnosis from either the initial presentation or at the time of recurrence is required for all but brain stem gliomas
- •Karnofsky or Lansky ≥ 60%
- •Life expectancy > 8 weeks
- •Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to study entry
- •Chemotherapy: No more than 2 previous chemotherapy/biologic therapy regimens; evidence of recovery from prior chemotherapy/biologic therapy; no myelosuppressive chemotherapy within 3 weeks (6 weeks if a nitrosourea agent) of study entry; patients who have received temozolomide are eligible if they have not received the drug in the past 3 months and did not experience any non-hematopoietic Grade 3/4 toxicity with prior temozolomide therapy
- •XRT: ≥ 3 months prior to study entry for craniospinal irradiation (≥ 18 Gy); ≥ 4 weeks for local radiation to primary tumor; and ≥ 2 weeks prior to study entry for focal irradiation to symptomatic metastatic sites
- •Bone Marrow Transplant: ≥ 6 months prior to study entry
- •Anti-convulsants: Patients will be eligible for this study even if they are receiving anti-convulsants
- •Growth factors: Off all colony forming growth factor(s) > 2 weeks prior to study entry (G-CSF, GM-CSF, Erythropoietin)
- •Dexamethasone: Patients who are receiving dexamethasone must be on a stable dose for at least 1 week prior to study entry
- •ANC > 1,000/μl
- •Platelets > 100,000/μl
- •Hemoglobin > 8g/dl
- •Patients may have bone marrow involvement by disease; platelet and Hgb counts must be transfusion independent
- •Creatinine ≤ 1.5 times institutional normal for age
- •Or GFR > 70 ml/min/1.73m^2
- •Bilirubin ≤ upper limit of normal for age
- •SGPT (ALT) < and SGOT (AST) < 2.5X institutional normal
- •No overt renal, hepatic, cardiac or pulmonary disease
- •Female patients of childbearing potential must have negative serum or urine pregnancy test; patient must not be pregnant or breast-feeding; while no known teratogenic effects are known for O6-BG so far, there is little data to address this specifically; as such, the prudent approach is to exclude pregnant and breastfeeding patients until further data is available
- •Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study
- •Signed informed consent according to institutional guidelines must be obtained and patients must begin therapy within seven (7) days of registration
排除标准
- •Patients must not be receiving any other anticancer or experimental drug therapy
- •Patients with a history of hypersensitivity to dacarbazine, temozolomide or polyethylene glycol are excluded
研究组 & 干预措施
Treatment (temozolomide, O6-benzylguanine)
See Detailed Description
干预措施: O6-benzylguanine (Drug)
Treatment (temozolomide, O6-benzylguanine)
See Detailed Description
干预措施: temozolomide (Drug)
Treatment (temozolomide, O6-benzylguanine)
See Detailed Description
干预措施: filgrastim (Biological)
Treatment (temozolomide, O6-benzylguanine)
See Detailed Description
干预措施: pharmacological study (Other)
Treatment (temozolomide, O6-benzylguanine)
See Detailed Description
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
MTD of temozolomide
时间窗: 28 days
次要结局
- Acute toxicities(4 weeks (course 1))
- Pharmacokinetic parameters(Baseline and courses 1 and 3)
- Chronic toxicities(Up to 30 days post-treatment)
- Survival(Up to 5 years)
- Histological response(Up to 5 years)
- Duration of disease control(Up to 5 years)