A Phase I Study of Single Agent OSI-774 (Tarceva) (NSC# 718781, IND# 63383) Followed by OSI-774 With Temozolomide for Patients With Selected Recurrent/Refractory Solid Tumors, Including Brain Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 95
- 试验地点
- 1
- 主要终点
- Maximum-tolerated dose (MTD) based on the incidence of DLT as assessed by NCI CTCAE version 3.0
研究概览
简要总结
This phase I trial is studying the side effects and best dose of erlotinib when given with temozolomide in treating young patients with recurrent or refractory solid tumors. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving erlotinib with temozolomide may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of erlotinib in children with recurrent or refractory solid tumors.
II. Determine the dose-limiting toxic effects of this drug alone and with temozolomide in these patients.
III. Determine the tolerability of this regimen in these patients. IV. Determine the pharmacokinetics of this regimen in these patients.
SECONDARY OBJECTIVES:
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
- •One of the following histologically confirmed solid tumors:
- •Brain tumors
- •Osteogenic sarcoma
- •Rhabdomyosarcoma
- •Soft tissue sarcoma (excluding Ewing's sarcoma)
- •Neuroblastoma
- •Germ cell tumors
- •Recurrent or refractory disease
- •No known curative therapy exists
- •Performance status - Karnofsky 50-100% (for patients age 11 to 21)
- •Performance status - Lansky 50-100% (for patients age 10 and under)
- •At least 8 weeks
- •Absolute neutrophil count > 1,000/mm^3
- •Platelet count > 100,000/mm^3 (transfusion independent*)
- •Hemoglobin > 8.0 g/dL (transfusion allowed)
- •Bilirubin < 1.5 times upper limit of normal (ULN)
- •ALT < 2.5 times ULN
- •Albumin ≥ 2 g/dL
- •Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
- •Creatinine based on age as follows:
- •≤ 0.8 mg/dL for patients age 5 and under
- •≤ 1.0 mg/dL for patients 6 to 10
- •≤ 1.2 mg/dL for patients 11 to 15
- •≤ 1.5 mg/dL for patients age 15 to 21
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Able to swallow tablets (for patients in part 2 only)
- •No uncontrolled infection
- •Recovered from all prior immunotherapy
- •At least 7 days since prior biologic therapy
- •At least 3 months since prior stem cell transplantation and no evidence of active graft-versus-host disease
- •More than 1 week since prior growth factors
- •No concurrent prophylactic growth factor therapy
- •No concurrent immunotherapy
- •No concurrent biologic therapy
- •More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
- •No other concurrent chemotherapy
- •No concurrent systemic corticosteroids except for treatment of increased intracranial pressure or symptomatic tumor edema in patients with CNS tumors
- •No concurrent steroids as an antiemetic
- •Concurrent dexamethasone for patients with CNS tumors allowed provided patient has been on a stable or decreasing dose for at least 1 week before study entry
- •Recovered from all prior radiotherapy
- •At least 2 weeks since prior local palliative radiotherapy (small port)
- •At least 6 weeks since prior substantial bone marrow irradiation
- •At least 6 months since prior craniospinal radiotherapy
- •At least 6 months since prior radiotherapy to 50% or more of the pelvis
- •At least 8 weeks since prior standard-fraction radiotherapy for patients with recurrent brain tumors unless there is biopsy proof of recurrent tumor
- •Prior radiosurgery within the past 9 months allowed provided there is documentation of progressive disease by biopsy, positron-emission tomography (PET) scan, or MR spectroscopy
- •No concurrent radiotherapy
- •More than 1 week since prior CYP3A4 inhibitors
- 另有 9 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (erlotinib hydrochloride, temozolomide)
Patients receive oral erlotinib once daily on days 1-28. Beginning with course 2, patients also receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 23 courses in the absence of disease progression or unacceptable toxicity.
干预措施: erlotinib hydrochloride (Drug)
Treatment (erlotinib hydrochloride, temozolomide)
Patients receive oral erlotinib once daily on days 1-28. Beginning with course 2, patients also receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 23 courses in the absence of disease progression or unacceptable toxicity.
干预措施: temozolomide (Drug)
Treatment (erlotinib hydrochloride, temozolomide)
Patients receive oral erlotinib once daily on days 1-28. Beginning with course 2, patients also receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 23 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Treatment (erlotinib hydrochloride, temozolomide)
Patients receive oral erlotinib once daily on days 1-28. Beginning with course 2, patients also receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 23 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Maximum-tolerated dose (MTD) based on the incidence of DLT as assessed by NCI CTCAE version 3.0
时间窗: 56 days (2 courses)
Dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
时间窗: 56 days (2 courses)
Pharmacokinetics of erlotinib hydrochloride
时间窗: At baseline and at 0.5, 1, 2, 4, 6, 8, and 24 hours of course 1
次要结局
未报告次要终点