NCT00020150已完成1 期
Phase I Trial and Pharmacokinetic Study of Temozolomide and O6-Benzylguanine in Childhood Solid Tumors
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 试验地点
- 1
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. Combining more than one drug may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of combining temozolomide and O6-benzylguanine in treating children who have solid tumors that have not responded to previous therapy.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of temozolomide administered with a biologically active dose of O6-benzylguanine (O6-BG) in children with refractory solid tumors.
- Determine the dose-limiting toxicity and the toxicity profile of this combination in these patients.
- Assess the plasma pharmacokinetics of O6-BG and its active metabolite, 8-oxo-O6-BG, in these patients.
- Assess the plasma pharmacokinetics of this combination in these patients.
- Correlate levels of alanine-glyoxylate aminotransferase in peripheral blood mononuclear cells with the degree of hematologic toxicity of this combination in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive O6-benzylguanine (O6-BG) IV over 1 hour followed 30 minutes later by oral temozolomide daily for 5 days. Treatment continues every 28 days for up to 12 courses in the absence of unacceptable toxicity or disease progression.
Sequential dose escalation of O6-BG is followed by sequential dose escalation of temozolomide. Cohorts of 3-6 patients receive escalating doses of O6-BG and temozolomide until the maximum tolerated dose (MTD) of each is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 6 patients experience dose-limiting toxicity.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed solid tumor refractory to standard therapy and for which no potentially curative therapy exists, including, but not limited to:
- •Rhabdomyosarcoma and other soft tissue sarcomas
- •Ewing's family of tumors
- •Osteosarcoma
- •Neuroblastoma
- •Wilms' tumor
- •Hepatic tumors
- •Germ cell tumors
- •Primary brain tumor
- •Histological confirmation may be waived for brainstem or optic gliomas
- •Measurable or evaluable disease
- •Evidence of progressive disease on prior chemotherapy or radiotherapy or persistent disease after prior surgery
- •PATIENT CHARACTERISTICS:
- •21 and under
- •Performance status:
- •Life expectancy:
- •At least 8 weeks
- •Hematopoietic:
- •Absolute granulocyte count greater than 1,500/mm^3
- •Hemoglobin greater than 8 g/dL
- •Platelet count greater than 100,000/mm^3
- •Bilirubin normal
- •SGPT less than 2 times upper limit of normal
- •No significant hepatic dysfunction
- •Creatinine normal OR
- •Creatinine clearance at least 60 mL/min
- •Cardiovascular:
- •No significant cardiac dysfunction
- •No significant pulmonary dysfunction
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Able to swallow capsules
- •No significant unrelated systemic illness that would preclude study (e.g., serious infections or organ dysfunction)
- •No prior hypersensitivity to dacarbazine, temozolomide, or polyethylene glycol
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •At least 1 week since prior colony-stimulating factors (e.g., filgrastim [G- CSF], sargramostim [GM-CSF], or epoetin alfa)
- •At least 4 months since prior myeloablative therapy requiring bone marrow or stem cell transplantation
- •No concurrent anticancer immunotherapy
- •Chemotherapy:
- •See Disease Characteristics
- •At least 3 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered
- •Prior temozolomide allowed provided not administered within past 3 months, no severe toxicities experienced during prior course, and not given in combination with other agents designed to inactivate alanine-glyoxylate aminotransferase
- •No other concurrent investigational or standard anticancer chemotherapy
- •Endocrine therapy:
- •Concurrent corticosteroids for control of brain tumor-associated edema allowed provided on stable or decreasing dose for at least 1 week prior to study
- •Radiotherapy:
- •See Disease Characteristics
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排除标准
- 未提供
研究者
研究点 (1)
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