Cilengitide (EMD121974) in Combination With Whole Brain Radiotherapy in Patients With Brain Metastases From Lung Cancer - a Single-center, Open-label Phase I Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity
研究概览
简要总结
RATIONALE: Cilengitide may stop the growth of brain metastases by blocking blood flow to the tumor. Radiation therapy uses high energy X-rays to kill tumor cells. Giving cilengitide together with radiation therapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of cilengitide when given together with whole-brain radiation therapy in treating patients with brain metastases from lung cancer.
详细描述
OBJECTIVES:
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Primary
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To assess the safety and tolerability of daily cilengitide by determining its dose-limiting toxicity and maximum-tolerated dose when combined with concomitant fractionated whole-brain radiation therapy in patients with brain metastases from lung cancer.
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Secondary
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To collect evidence of the best overall response rate, overall survival, brain-specific progression-free survival, and tumor-specific progression-free survival of these patients.
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To collect evidence of changes in functional MRI imaging studies at 6 and 12 weeks after initiation of therapy.
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To collect evidence of early response by functional MRI (ASL technique) on days 1, 4, and 12, immediately before and after the administration of cilengitide.
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To collect evidence of changes in neurological and neurocognitive function tests at 6 and 12 weeks after initiation of therapy.
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To further evaluate the safety and toxicity of the combination of cilengitide and whole-brain radiation therapy.
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To further evaluate the pharmacokinetics of cilengitide administered daily.
OUTLINE:
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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed lung cancer (small cell or non-small cell lung cancer)
- •Patient must be eligible for whole-brain radiotherapy
- •Presence of brain metastasis (single or multiple, synchronous or metachronous) from lung cancer not amenable to surgery or radiosurgery (presence of metastases at any other site is allowed)
- •No leptomeningeal metastasis or known subarachnoid spread of tumor
- •PATIENT CHARACTERISTICS:
- •ECOG performance status (PS) 0-1 (ECOG PS 2 allowed if due to the presence of cerebral metastases and not due to a high peripheral-tumor load or other reasons)
- •Life expectancy ≥ 3 months
- •Adequate hematologic function
- •Total bilirubin < 1.5 times upper limit of normal (ULN)
- •AST, ALT, and alkaline phosphatase < 2.5 times ULN
- •Creatinine clearance > 60 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 6 months after completion of study treatment
- •No history of acute or chronic renal disease
- •No other malignancies treated within the past 5 years, except adequately treated carcinoma in situ of the cervix or basal cell carcinoma of the skin
- •No uncontrolled hypertension
- •No history of coagulation disorder associated with bleeding or recurrent thrombotic events
- •No peptic ulcer disease within the past 6 months
- •No congestive heart failure, high risk for uncontrolled arrhythmia, or history of clinically significant coronary heart disease
- •No known alcohol or drug abuse
- •No other significant or acute concomitant disease
- •No dementia or altered mental status
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •Concurrent corticosteroids allowed if the dosing regimen has ben stable ≥ 5 days
- •Concurrent anticonvulsants allowed if the dosing regimen has been stable for the past week
- •More than 30 days since prior participation in another clinical trial
- •No concurrent anticoagulation with vitamin K antagonists, therapeutic-dose anticoagulation with heparin resulting in prolonged PTT, or therapeutic-dose anticoagulation with low molecular weight heparin (low-dose [i.e. prophylactic], low molecular weight heparins allowed)
- •No prior whole-brain radiation or radiosurgery
- •No prior antiangiogenic therapy
- •No other concurrent anticancer therapy
排除标准
- 未提供
研究组 & 干预措施
Cilengitide
干预措施: cilengitide (Drug)
Cilengitide
干预措施: pharmacological study (Other)
Cilengitide
干预措施: radiation therapy (Radiation)
结局指标
主要结局
Dose-limiting toxicity
时间窗: 12 days
(i) Any grade III-IV non-hematological toxicity as defined by CTCAE, version 3.0, with the exclusion ofalopecia, nausea, vomiting, and fever that can be rapidly contolled with appropriate measures; (ii) absolute neutrophil count (ANC)\<0.5x10'/L lasting for \>7days; (iii) febrile neutropenia defined as ANC \<1.0x10'/L and fever \>38.5°C; (iv) platelets \<25x10'/L or thrombocytopenic bleeding requiring transfusion; and (v) severe hypotension requiring dopamine administration.
Maximum-tolerated dose
时间窗: 12 days
5 planned steps to be tested: 100, 250, 500, 750, to 1000mg; the highest dose at which one or no DLT will have been observed among 6 patients
次要结局
- Brain-specific progression-free survival (PFS)(1 year)
- Changes in functional MRI imaging (blood flow) at 6 and 12 weeks(12 weeks)
- Evidence of early response by functional MRI on days 1, 4, and 12(12 days)
- Changes of neurocognitive function tests (intelligence) at 6 and 12 weeks(12 weeks)
- Changes of neurocognitive function tests (attention/alertness) at 6 and 12 weeks(12 weeks)
- Changes of neurocognitive function tests (attention) at 6 and 12 weeks(12 weeks)
- Changes of neurocognitive function tests (attention speaking) at 6 and 12 weeks(12 weeks)
- Activities of daily living (Barthel) at 6 and 12 weeks(12 weeks)
- Activities of daily living (instrumental) at 6 and 12 weeks(12 weeks)
- Tumor-specific PFS(1 year)
- Overall response rate(12 weeks)
- Overall survival(1 year)
- Changes of neurocognitive function tests (memory verbal) at 6 and 12 weeks(12 weeks)
- Fatigue at 6 and 12 weeks(12 weeks)
- Changes in functional MRI imaging (time to peak) at 6 and 12 weeks(12 weeks)
- Changes in functional MRI imaging (blood volume changes) at 6 and 12 weeks(12 weeks)
- Changes of neurocognitive function tests (memory figures) at 6 and 12 weeks(12 weeks)
- Changes of neurocognitive function tests (perception) at 6 and 12 weeks(12 weeks)
- Anxiety/depression at 6 and 12 weeks(12 weeks)
研究者
Frederik Wenz
Prof. Christian Manegold
Universitätsmedizin Mannheim