A Phase I Study of EMD 121974 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- MTD of cilengitide defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
研究概览
简要总结
Phase I trial to study the effectiveness of EMD 121974 in treating patients who have advanced solid tumors. EMD 121974 may slow the growth of solid tumors by stopping blood flow to the tumor
详细描述
OBJECTIVES:
I. Determine the toxic effects and maximum tolerated dose of EMD 121974 in patients with advanced solid tumors.
II. Determine the biologic activity of this drug in these patients. III. Determine the pharmacokinetic profile and plasma biological effects of this drug and identify any relationship with its biologic activity or observed toxicity in these patients.
IV. Determine, preliminarily, the antitumor efficacy of this drug in these patients.
OUTLINE: This is a dose-escalation 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 confirmed solid tumor that is refractory to standard therapy or for which no standard therapy exists
- •Tumors must be amenable to minimally-invasive biopsy (i.e., tumors must be superficial enough to be sampled by punch biopsy or core biopsy procedure without radiologic guidance)*
- •No uncontrolled brain metastases, including symptomatic lesions or lesions requiring glucocorticoids and/or anticonvulsants to suppress symptoms
- •Negative brain scan required if there are signs and symptoms suggestive of brain metastasis
- •Performance status - ECOG 0-2
- •Performance status - Karnofsky 60-100%
- •At least 12 weeks
- •WBC at least 3,000/mm^3
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Hemoglobin at least 9 g/dL
- •Bilirubin normal
- •AST and ALT no greater than 2.5 times upper limit of normal
- •Creatinine normal
- •Creatinine clearance at least 60 mL/min
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No ongoing or active infection
- •No other concurrent serious systemic disorders (e.g., significant CNS illness) that would preclude study
- •No concurrent psychiatric illness or social situations that would preclude study
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No other concurrent anticancer immunotherapy
- •Concurrent hematologic growth factors for cytopenias allowed
- •At least 4 weeks since prior anticancer chemotherapy (6 weeks for nitrosoureas, carmustine, or mitomycin) and recovered
- •See Disease Characteristics
- •No concurrent anticancer hormonal therapy
- •Concurrent oral contraceptives or postmenopausal hormone replacement allowed
- •Recovered from prior radiotherapy
- •At least 2 weeks since prior palliative radiotherapy to bone or brain metastases
- •At least 4 weeks since prior anticancer radiotherapy
- •No concurrent anticancer radiotherapy
- •Not specified
- •At least 4 weeks since prior anticancer therapy and recovered
- •At least 4 weeks since prior investigational agents
- •Any number of prior therapies allowed
- •No other concurrent anticancer investigational or commercial agents
- •No concurrent combination antiretroviral therapy for HIV-positive patients
排除标准
- 未提供
研究组 & 干预措施
Treatment (cilengitide)
Patients receive EMD 121974 IV over 1 hour twice weekly. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: cilengitide (Drug)
Treatment (cilengitide)
Patients receive EMD 121974 IV over 1 hour twice weekly. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Treatment (cilengitide)
Patients receive EMD 121974 IV over 1 hour twice weekly. Courses repeat every 4 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
MTD of cilengitide defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
时间窗: 4 weeks
Graded according to the NCI Common Toxicity Criteria version 2.0.
Toxic effects of cilengitide described as an adverse event that has an attribution of possibly, probably or definitely related to investigational treatment
时间窗: Up to 4 years
Graded according to the NCI Common Toxicity Criteria version 2.0.
Biological activity of this regimen
时间窗: Up to 4 years
Measured buy TUNEL assay, CD31 immunohistochemistry, dynamic contrast-enhanced MRI, and FDG-PET scan.
次要结局
- Pharmacokinetics of cilengitide(At 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 8.0, and 24.0 hours post-end-of-infusion on day 1 of course 1)
- Observation of response consisting of complete response, partial response, or stable disease, evaluated using the RECIST criteria(Up to 4 years)
- Time to progression(Up to 4 years)