Epothilone ZK-219477 in Treating Patients With Recurrent Glioblastoma
Phase II Study of ZK 219477 in Patients With Recurrent Glioblastoma
RATIONALE: Drugs used in chemotherapy, such as epothilone ZK-219477, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This phase II trial is studying how well epothilone ZK-219477 works in treating patients with recurrent glioblastoma.
研究概览
详细说明
OBJECTIVES:
Primary
- Assess the therapeutic activity of epothilone ZK-219477 in patients with recurrent glioblastoma.
Secondary
- Determine the safety profile, mechanism of action, and pharmacokinetics of this drug in these patients.
- Gather information about the biological characteristics of the patients' tumor that may provide information on response or resistance to this drug.
OUTLINE: This is a nonrandomized, open-label, multicenter study.
Patients receive epothilone ZK-219477 IV over 3 hours on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline for biomarker analysis and for comparison of genetic alterations in tumor tissue with germline DNA. Blood samples are also collected periodically during course 1 for pharmacokinetic studies. Tumor tissue obtained at diagnosis, and possibly recurrence, is used for immunohistochemical analyses for biomarkers. Fluorescent in situ hybridization (FISH) is used to detect genetic alterations and gene expression.
After completion of study treatment, patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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Lausanne、瑞士、CH-1011
- Centre Hospitalier Universitaire Vaudois
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
DISEASE CHARACTERISTICS:
Histologically confirmed glioblastoma
- Presence of oligodendroglial elements allowed provided they make up < 25% of tumor
- Measurable disease, defined as ≥ 1 bidimensionally measurable target lesion with a largest diameter of ≥ 2 cm by MRI within the past 2 weeks
Recurrent disease
- Documented by MRI after failing prior therapy (usually standard radiotherapy with concurrent and maintenance temozolomide)
- Subsequent histologic confirmation of recurrence required for patients who received prior high-dose radiotherapy (> 65 Gy), stereotactic radiosurgery, or internal radiotherapy
- Multifocal disease that is not amenable to radiotherapy allowed provided the patient received no more than 1 line of prior chemotherapy
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Bilirubin < 1.5 times upper limit of normal (ULN)
- AST and ALT < 2.5 times ULN
- Alkaline phosphatase < 2.5 times ULN
- Creatinine < 1.5 times ULN
- Clinically normal cardiac function
No ischemic heart disease within the past 12 months
- Stable ischemic heart disease (e.g., treated angina that is stable under appropriate therapy) allowed
- No New York Heart Association class III or IV cardiac insufficiency
- No unstable angina
- No arrhythmia
- No psychological, familial, sociological, or geographical factors that would preclude study compliance
- No other malignancy except cone-biopsied carcinoma of the cervix or adequately treated basal cell or squamous cell skin cancer
- Not pregnant or nursing
- Negative pregnancy test
- Fertile female patients must use effective contraception during and for 3 months after completion of study treatment
- Fertile male patients must use effective contraception during and for 6 months after completion of study treatment
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
- More than 3 months since prior radiotherapy to the brain
More than 3 months since prior surgery for recurrent primary brain tumor unless 1 of the following criteria are met:
- Measurable residual disease documented by immediate (within 72 hours) postoperative imaging
- Evidence of a progressive and measurable target lesion found at postoperative follow-up
- Presence of a second measurable target lesion outside the surgical area
- Prior adjuvant temozolomide as first-line therapy allowed
No prior chemotherapy for recurrent glioblastoma
- One prior chemotherapy regimen given as adjuvant therapy allowed
- Concurrent corticosteroids allowed provided dose is stable or decreasing for ≥ 1 week
- No concurrent phenytoin, carbamazepine, or phenobarbital
- No concurrent Hypericum perforatum (St. John's wort)
No concurrent enzyme-inducing antiepileptic drugs (EIAEDs)
- Patients on EIAEDs should have been switched to non-EIAEDs with a wash-out period of ≥ 1 month
- No other concurrent anticancer agents (except alternative or homeopathic medicine)
- No other concurrent investigational treatment
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 屏蔽:无(打开标签)
研究衡量的是什么?
主要结果指标
结果测量 |
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Treatment success (complete or partial response or a progression-free survival at 6 months)
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次要结果测量
结果测量 |
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客观反应
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毒性
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反应持续时间
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6 个月无进展生存期
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Overall survival at 6 and 12 months
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合作者和调查者
出版物和有用的链接
一般刊物
- Stupp R, Tosoni A, Bromberg JEC, Hau P, Campone M, Gijtenbeek J, Frenay M, Breimer L, Wiesinger H, Allgeier A, van den Bent MJ, Bogdahn U, van der Graaf W, Yun HJ, Gorlia T, Lacombe D, Brandes AA. Sagopilone (ZK-EPO, ZK 219477) for recurrent glioblastoma. A phase II multicenter trial by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group. Ann Oncol. 2011 Sep;22(9):2144-2149. doi: 10.1093/annonc/mdq729. Epub 2011 Feb 14.
- Stupp R, Tosoni W, Taal W, et al.: Phase II trial of the epothilone analog sagopilone (ZK219477; ZK EPO) in patients with recurrent glioblastoma: initial report of the EORTC study 26061. [Abstract] J Clin Oncol 26 (Suppl 15): A-2015, 2008.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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