Phase I/II Study of Obatoclax Mesylate (GX15-070MS), a Bcl-2 Antagonist, Plus Topotecan in Relapsed Small Cell Lung Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 2
- 主要终点
- Overall Response Rate (Phase II)
研究概览
简要总结
This phase I/II trial is studying the side effects and best dose of obatoclax mesylate when given together with topotecan hydrochloride and to see how well they work in treating patients with relapsed or refractory small cell lung cancer or advanced solid tumors. Obatoclax mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving obatoclax mesylate together with topotecan hydrochloride may help kill more tumor cells
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose, recommended phase II dose, and toxicity profile of obatoclax mesylate when administered with topotecan hydrochloride in patients with advanced solid tumors. (Phase I) II. Determine the response rate in patients with relapsed or refractory small cell lung cancer treated with obatoclax mesylate and topotecan hydrochloride. (Phase II)
SECONDARY OBJECTIVES:
I. Evaluate the expression of pro- and anti-apoptotic proteins which may correlate with obatoclax mesylate sensitivity or resistance.
OUTLINE: This is a phase I dose-escalation study of obatoclax mesylate followed by a phase II study.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed diagnosis of 1 of the following:
- •Advanced solid tumor (phase I)
- •Topotecan hydrochloride must be an appropriate treatment for this cancer
- •Small cell lung cancer (SCLC) (phase II)
- •Progressed after one prior platinum-based chemotherapy regimen
- •Pathology materials (tumor tissue) will be used for correlative studies, if available
- •No progressive brain metastases
- •Treated brain metastases allowed provided patient is neurologically stable and does not require steroids
- •No leptomeningeal involvement
- •ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
- •Leukocytes ≥ 3,000/mcL
- •Absolute neutrophil count ≥ 1,500/mcL
- •Platelet count ≥ 100,000/mcL
- •Total bilirubin normal
- •AST and ALT ≤ 2.5 times upper limit of normal
- •Creatinine normal OR creatinine clearance ≥ 60 mL/min
- •Not pregnant or nursing
- •Fertile patients must use effective double barrier method of contraception during and for 3 months after completion of study therapy
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
- •At least 4 weeks since prior radiotherapy and recovered
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No other concurrent investigational agents or anticancer therapy
排除标准
- •History of allergic reactions attributed to compounds of similar chemical or biological composition to obatoclax mesylate or topotecan hydrochloride (e.g., irinotecan)
- •Concurrent uncontrolled illness including, but not limited to, any of the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Psychiatric illness or social situations that would limit compliance with study requirements
- •History of seizure disorder or other neurological dysfunction (except peripheral neuropathy)
研究组 & 干预措施
Treatment (enzyme inhibitor therapy and chemotherapy)
Patients receive obatoclax mesylate IV over 3 hours on day 1 OR days 1 and 3 and topotecan hydrochloride IV over 30 minutes on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity
干预措施: obatoclax mesylate (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
Patients receive obatoclax mesylate IV over 3 hours on day 1 OR days 1 and 3 and topotecan hydrochloride IV over 30 minutes on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity
干预措施: topotecan hydrochloride (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
Patients receive obatoclax mesylate IV over 3 hours on day 1 OR days 1 and 3 and topotecan hydrochloride IV over 30 minutes on days 1-5. Courses repeat every 3 weeks 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
Overall Response Rate (Phase II)
时间窗: Every 6 weeks, assessed up to 30 days
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR +PR
次要结局
未报告次要终点