A Phase I Study Of BG In Combination With Ifosfamide For Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Change in degree of myelosuppression (thrombocytopenia and neutropenia) quantified by both duration of neutropenia and severity of neutropenia
研究概览
简要总结
This randomized phase I trial is studying the side effects and best dose of O(6)-benzylguanine when given together with ifosfamide and to see how well it works compared to ifosfamide alone in treating patients with unresectable metastatic solid tumors. Drugs used in chemotherapy, such as ifosfamide and O(6)-benzylguanine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining ifosfamide with O(6)-benzylguanine may kill more tumor cells
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of O6-benzylguanine when administered with standard high-dose ifosfamide in patients with unresectable, metastatic solid tumors.
II. Determine whether O6-benzylguanine enhances ifosfamide-mediated myelosuppression in patients treated with this regimen.
III. Determine the relationship between O6-benzylguanine dose and intra-individual variability in the degree of myelosuppression in patients treated with this regimen.
IV. Determine the safety and toxicity of this regimen in these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed solid tumor
- •Unresectable, metastatic disease
- •No primary tumors
- •Eligible for high-dose ifosfamide-based therapy
- •No known brain metastases
- •Performance status - ECOG 0-1
- •Performance status - Karnofsky 70-100%
- •More than 12 weeks
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •AST and ALT ≤ 2.5 times upper limit of normal
- •Bilirubin normal
- •Creatinine normal
- •Creatinine clearance ≥ 60 mL/min
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 4 weeks after study participation
- •No history of allergic reaction attributed to compounds of similar chemical or biological composition to O6-benzylguanine or other study agents
- •No concurrent uncontrolled illness
- •No active or ongoing infection
- •No psychiatric illness or social situation that would preclude study compliance
- •More than 24 hours since prior colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF])
- •No prior hematopoietic stem cell transplantation
- •No concurrent pegfilgrastim
- •No concurrent immunotherapy
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •No other concurrent chemotherapy
- •No concurrent hormonal therapy
- •More than 4 weeks since prior radiotherapy and recovered
- •No concurrent therapeutic radiotherapy
- •More than 4 weeks since prior anticancer therapy
- •No more than 2 prior cytotoxic regimens
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No other concurrent anticancer agents or therapies
- •No other concurrent investigational agents
排除标准
- 未提供
研究组 & 干预措施
Arm I (ifosfamide)
Patients receive high-dose ifosfamide IV continuously over 72 hours on days 1-3.
干预措施: ifosfamide (Drug)
Arm II (O6-benzylguanine, ifosfamide)
Patients receive a bolus dose of O6-benzylguanine (BG) IV over 1 hour on day 1 followed by BG IV continuously and high-dose ifosfamide IV continuously over 72 hours on days 1-3.
干预措施: ifosfamide (Drug)
Arm II (O6-benzylguanine, ifosfamide)
Patients receive a bolus dose of O6-benzylguanine (BG) IV over 1 hour on day 1 followed by BG IV continuously and high-dose ifosfamide IV continuously over 72 hours on days 1-3.
干预措施: O6-benzylguanine (Drug)
结局指标
主要结局
Change in degree of myelosuppression (thrombocytopenia and neutropenia) quantified by both duration of neutropenia and severity of neutropenia
时间窗: Baseline up to 1 year
Maximum tolerated dose (MTD) of O6-benzylguanine defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience dose-limiting toxicity
时间窗: 21 days
DLT is defined as any \>= grade 3 non-hematologic toxicity, grade 4 thrombocytopenia, or prolonged neutropenia.
次要结局
- Pharmacodynamics including apoptosis and DNA damage(Up to 1 year)
- Pharmacokinetics of O6-benzylguanine(Up to day 3 of course 2)