A Phase I Dose Escalation Study of Intravenous DX-8951f Administered Daily for Five Days Every Three Weeks to Pediatric Patients With Advanced Solid Tumors and Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 试验地点
- 7
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.
PURPOSE: Phase I trial to study the effectiveness of DX-8951f in treating children who have advanced solid tumors or lymphomas that have not responded to previous therapy.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of exatecan mesylate (DX-8951f) with and without filgrastim (G-CSF) in pediatric patients with advanced solid tumors or lymphomas.
- Determine the toxic effects, including dose-limiting toxicity, of exatecan mesylate in these patients.
- Determine the pharmacokinetics of exatecan mesylate in these patients.
- Determine the recommended dose of exatecan mesylate for phase II study.
- Determine the antitumor activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study of exatecan mesylate (DX-8951f). Patients are stratified according to prior treatment (minimally treated vs heavily treated).
Patients receive exatecan mesylate IV over 30 minutes daily for 5 days. Patients in dose levels 5 and above also receive filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing for at least 7 days or until blood counts recover. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 1-6 patients receive escalating doses of exatecan mesylate with and without G-CSF until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 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 advanced solid tumors, including brain tumors and lymphomas, that have failed standard therapy (surgery, radiotherapy, endocrine therapy, or chemotherapy) or for which no standard therapy exists
- •Histology requirement waived for brain stem gliomas
- •PATIENT CHARACTERISTICS:
- •21 and under at diagnosis
- •Performance status:
- •Life expectancy:
- •At least 8 weeks
- •Hematopoietic:
- •Absolute neutrophil count at least 750/mm^3
- •Platelet count at least 75,000/mm^3
- •Hemoglobin at least 8.5 g/dL
- •Bilirubin no greater than 1.5 mg/dL
- •SGOT or SGPT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases)
- •Creatinine no greater than 1.5 times ULN OR
- •GFR at least 70 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •No history of severe or life-threatening hypersensitivity to camptothecin analogs
- •HIV negative
- •No other concurrent severe or uncontrolled medical illness
- •No systemic infection
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •Recovered from prior immunotherapy
- •Chemotherapy:
- •See Disease Characteristics
- •Recovered from prior chemotherapy
- •Endocrine therapy:
- •See Disease Characteristics
- •Radiotherapy:
- •See Disease Characteristics
- •At least 4 weeks since prior extensive radiotherapy involving cranial, whole pelvic, or at least 25% of bone marrow reserve
- •Recovered from prior radiotherapy
- •Concurrent localized radiotherapy for pain allowed
- •See Disease Characteristics
- •Recovered from prior surgery
- •No other concurrent antitumor therapy
- •No concurrent drugs that induce or inhibit CYP3A enzyme
排除标准
- 未提供