An Open-Label, Multicenter, Phase 1 Dose Escalation Study to Evaluate Safety, Tolerability and Anti-tumor Activity of Systemic Buthionine Sulfoximine (BSO) in Combination With Normothermic Isolated Limb Infusion of Melphalan in Subjects With Locally Advanced In-Transit Malignant Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 4
- 主要终点
- Maximum tolerated dose of melphalan when administered as an isolated limb infusion in combination with a systemic infusion of buthionine sulfoximine (BSO)
研究概览
简要总结
RATIONALE: Buthionine sulfoximine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sometimes when chemotherapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to chemotherapy. Giving buthionine sulfoximine together with chemotherapy may reduce drug resistance and allow the tumor cells to be killed.
PURPOSE: This phase I trial is studying the side effects and best dose of melphalan when given as an isolated limb infusion together with buthionine sulfoximine in treating patients with persistent or recurrent stage III malignant melanoma.
详细描述
OBJECTIVES:
Primary
- To determine the maximum tolerated dose of melphalan when administered as an isolated limb infusion in combination with a systemic infusion of buthionine sulfoximine (BSO) in patients with persistent or recurrent stage IIIB or IIIC in-transit malignant melanoma.
Secondary
- To define the dose-limiting toxicity of regional melphalan when administered with systemic BSO in these patients.
- To determine whether the combination of systemic BSO and regional melphalan can yield clinical responses in patients who have not responded well to prior melphalan-based regional treatment.
- To determine the effectiveness of systemic BSO in decreasing tumor glutathione (GSH) levels and its effect on GST activity and GST expression.
- To examine the correlation between tumor GSH levels and GSH levels in peripheral blood mononuclear cells to determine if the latter can serve as a surrogate marker for tumor GSH depletion.
- To determine the pharmacokinetics of systemic BSO and regional melphalan in these patients.
- To determine if BSO alters the mRNA expression signature of melphalan resistance.
- To determine, preliminarily, the efficacy of systemic BSO and regional melphalan in these patients.
- To correlate baseline mRNA expression signature of melphalan resistance with treatment efficacy.
研究设计
- 研究类型
- Interventional
- 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
- 未提供
排除标准
- 未提供
结局指标
主要结局
Maximum tolerated dose of melphalan when administered as an isolated limb infusion in combination with a systemic infusion of buthionine sulfoximine (BSO)
次要结局
- Clinical response
- Pharmacokinetics
- Dose-limiting toxicity of regional melphalan when administered with systemic BSO
- Efficacy as defined by the RECIST criteria modified for cutaneous lesions
- Effectiveness of systemic BSO in decreasing tumor glutathione (GSH) levels and its effect on GST activity and GST expression
- Correlation between tumor GSH levels and GSH levels in peripheral blood mononuclear cells to determine if the latter can serve as a surrogate marker for tumor GSH depletion
- mRNA expression signature of melphalan resistance
- Correlation of baseline mRNA expression signature of melphalan resistance with treatment efficacy