A Phase 2 Trial of Tandutinib in Combination With Bevacizumab for Patients With Recurrent High-Grade Gliomas
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Progression-free Survival at 6 Months
研究概览
简要总结
Background:
In order to survive, brain tumors must have a network of blood vessels to supply it with oxygen and nutrients. The tumors produce substances that enable new blood vessels to form.
Tandutinib and Bevacizumab are experimental drugs that may prevent new blood vessel formation and thereby slow or stop tumor growth in the brain.
Objectives:
To determine the safety and side effects of Tandutinib in combination with Bevacizumab in patients with brain tumors.
To evaluate the response of brain tumors to treatment with Tandutinib and Bevacizumab.
Eligibility:
Patients 18 years of age and older with a malignant brain tumor for whom standard treatments (surgery, radiation and chemotherapy) are no longer effective.
Design:
Patients receive treatment in 4-week cycles as follows: Tandutinib by mouth twice a day every day and intravenous (through a vein) infusions of Bevacizumab over 90 minutes (or less if well tolerated) every 2 weeks. Treatment may continue for up to 1 year, and possibly longer, as long as there are no signs of tumor growth or serious treatment side effects.
Patients are evaluated with magnetic resonance imaging (MRI), computed tomography (CT) and positron emission tomography (PET) scans before starting treatment and then periodically to determine the response to treatment.
Patients have physical and neurological examinations every 4 weeks and blood tests every 2 weeks. They complete quality of life questionnaires every 4 weeks.
详细描述
Background
Bevacizumab is a monoclonal antibody directed against vascular- endothelial growth factor (VEGF), the major angiogenesis factor involved in high-grade glioma-mediated angiogenesis. Preclinical studies in our laboratory and others have shown potent antiglioma activity in vivo and early clinical trials of bevacizumab in combination with irinotecan and alone (National Institutes of Health (NIH) study) have demonstrated significant anti-vascular permeability and anti-glioma effects in patients with recurrent gliomas.
Tandutinib (MLN518) along with bevacizumab represents an attempt to further capitalize on the concept of targeting the tumor vasculature. Tandutinib is a small molecule inhibitor of fms-like tyrosine kinase receptor-3 (FLT3), platelet derived growth factor receptor (PDGFR), and cKIT (type III receptor tyrosine kinases). It has demonstrated anti-leukemic activity in patients with relapsed and refractory acute myeloid leukemia (AML) whose blasts contain an activating internal tandem duplication mutation of FLT3. However, in this study tandutinib is being added to bevacizumab primarily for its activity against the PDGFR and cKIT. Hannahan and colleagues have demonstrated the additional anti-tumor activity that results in vivo with combined inhibition of the vascular endothelial growth factor receptor (VEGFR) and PDGFR. The activity of PDGFR inhibition is hypothesized to result from its effect on pericytes, the cells that surround and support endothelial cells. These cells have abundant expression of PDGFR and require platelet-derived growth factor (PDGF)-PDGFR interaction for their normal function.
Objectives
To establish data regarding the anti-tumor activity of the combination of bevacizumab and tandutinib in patients with recurrent high-grade gliomas, as determined by progression-free-survival.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
研究组 & 干预措施
Tandutinib & Bevacizumab in GBM Patients
GBM (glioblastoma multiforme) Tandutinib 500 mg by mouth daily dose twice a day. Bevacizumab 10 mg/kg dose intravenous repeated once every 2 weeks.
干预措施: Bevacizumab (Biological)
Tandutinib & Bevacizumab in GBM Patients
GBM (glioblastoma multiforme) Tandutinib 500 mg by mouth daily dose twice a day. Bevacizumab 10 mg/kg dose intravenous repeated once every 2 weeks.
干预措施: MLN-518 (Tandutinib) (Drug)
Tandutinib & Bevacizumab in GBM Patients
GBM (glioblastoma multiforme) Tandutinib 500 mg by mouth daily dose twice a day. Bevacizumab 10 mg/kg dose intravenous repeated once every 2 weeks.
干预措施: Quality-of-life assessment (Procedure)
Tandutinib & Bevacizumab in AG Patients
AG (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed oligoastrocytoma, and malignant astrocytoma NOS (not otherwise specified)) Tandutinib 500 mg by mouth daily dose twice a day. Bevacizumab 10 mg/kg dose intravenous repeated once every 2 weeks.
干预措施: Bevacizumab (Biological)
Tandutinib & Bevacizumab in AG Patients
AG (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed oligoastrocytoma, and malignant astrocytoma NOS (not otherwise specified)) Tandutinib 500 mg by mouth daily dose twice a day. Bevacizumab 10 mg/kg dose intravenous repeated once every 2 weeks.
干预措施: MLN-518 (Tandutinib) (Drug)
Tandutinib & Bevacizumab in AG Patients
AG (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed oligoastrocytoma, and malignant astrocytoma NOS (not otherwise specified)) Tandutinib 500 mg by mouth daily dose twice a day. Bevacizumab 10 mg/kg dose intravenous repeated once every 2 weeks.
干预措施: Quality-of-life assessment (Procedure)
结局指标
主要结局
Progression-free Survival at 6 Months
时间窗: 6 months
Percentage of participants with progression free survival at 6 months. Progression is defined as a 25% increase in the sum of all measurable lesions (or two largest lesions if too numerous) over the smallest sum observed (over baseline if no decrease), clear worsening of any evaluable disease, appearance of any new lesion/site, or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
次要结局
- Number of Participants With Adverse Events(45 months)
研究者
Katherine E. Warren, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)