PHASE II STUDY OF BEVACIZUMAB PLUS IRINOTECAN (CAMPTORSAR) IN CHILDREN WITH RECR

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 贝伐单抗联合伊立替康将在复发的恶性胶质瘤和弥漫性脑干胶质瘤的儿童中进行II期研究。治疗将首先在第1天和第15天静脉注射单剂贝伐单抗10 mg/kg，然后在第二剂Begacizumab后24-48小时内进行MR灌注/扩散成像，以评估是否存在渗透性降低，因为血管内皮生长因子介导肿瘤血管生成和血管通透性，而贝伐单抗直接抑制血管内皮生长因子。第一剂伊立替康将在MR灌注扫描后静脉注射。随后，贝伐单抗和伊立替康将每两周服用一次。伊立替康的剂量将取决于患者是否在服用一种酶诱导的抗惊厥药物(EIACD)。接受EIACDS治疗的患者，伊立替康剂量为250 mg/m~2，每两周一次。如果患者没有接受EIACD治疗，起始剂量将为125 mg/m^2。这些剂量通常与伊立替康一起使用，作为成人和儿童恶性胶质瘤的单药。治疗将继续研究，直到肿瘤进展，不可接受的毒性，或最长两年。将在治疗前定期进行标准的脑部+/-脊椎MRI扫描、快速灌注和扩散MRI以及FDG-PET扫描，以研究贝伐单抗+伊立替康对这些肿瘤的疗效。此外，还将研究贝伐单抗的生物相关性，包括贝伐单抗的血清药代动力学、外周血单个核细胞上血管内皮生长因子受体-2的表达以及贝伐单抗对血管内皮生长因子-R2磷酸化的影响。后者可能与肿瘤反应和贝伐单抗治疗后肿瘤的MR灌注变化有关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A phase II study of bevacizumab in combination with irinotecan will be performed in children with recurrent malignant glioma and diffuse brain stem gliomas. Therapy will begin with single-agent bevacizumab 10 mg/kg given intravenously on day 1 and day 15 followed by MR-perfusion/diffusion imaging within 24-48 hours following the 2nd dose of begacizumab to assess whether there is reduction in permeability since VEGF mediates tumor angiogenesis and vascular permeability and bevacizumab directly inhibits VEGF. The first dose of irinotecan will be given intravenously following this MR-perfusion scan. Subsequently, bevacizumab and irinotecan will be given every two weeks. The irinotecan dose will depend on whether the patient is on an enzyme-inducing anticonvulsant drug (EIACD). The irinotecan dose will be 250 mg/m^2 every two weeks for those on EIACDS. If the patient is not on an EIACD, the starting dose will be 125 mg/m^2. These doses are routinely used with irinotecan is administered as a single-agent for malignant glioma in adults and children. Treatment will continue on study until tumor progression, unacceptable toxicity, or for a maximum if two years. Standard MRI scan of brain +/- spine, rapid perfusion and diffusion MRI, and FDG-PET scans prior to treatment and at periodic intervals will be obtained to study the effects of bevacizumab + irinotecan in these tumors. In addition, biology correlates will be studied including serum pharmacokinetics of bevacizumab and the expression of vacular endothelial growth factor receptor-2 on peripheral blood mononuclear cells and the effect of bevacizumab on VEGF-R2 phosphorylation. The latter would be correlated with tumor responses and MR perfusion changes in tumor following bevacizumab therapy.