CLINICAL TRIAL: PBTC-022 PHASE II STUDY OF BEVACIZUMAB PLUS IRINOTECAN (CAMPTOSA

临床试验：贝伐珠单抗加伊立替康 (CAMPTOSA) 的 PBTC-022 II 期研究

• 批准号: 8166687
• 负责人: SUSAN M. BLANEY
• 金额: $ 0.23万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166687
• 关键词: Brain Neoplasms; Brain Stem Glioma; Child; Childhood; Clinical Research; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Diffuse; Diffusion; Disease Progression; Disease-Free Survival; Dose; Down-Regulation; Drug Kinetics; Drug resistance; Funding; Glioma; Grant; Hour; Image; Incidence; Institution; Malignant - descriptor; Malignant Glioma; Mediating; Mediator of activation protein; Neoplasm Metastasis; Outcome; Patients; Perfusion; Peripheral Blood Mononuclear Cell; Permeability; Phase; Play; Randomized; Recurrence; Refractory; Research; Research Personnel; Resources; Role; Scanning; Serum; Source; Survival Rate; Toxic effect; Treatment Failure; Treatment Protocols; Tumor Angiogenesis; United States National Institutes of Health; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factors; angiogenesis; bevacizumab; chemotherapy; fluorodeoxyglucose positron emission tomography; improved; inhibitor/antagonist; irinotecan; novel strategies; outcome forecast; phase 3 study; pre-clinical; response; tumor; tumor growth

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. Bevacizumab in combination with irinotecan (CPT-11) will be well-tolerated and demonstrate objective tumor response in pediatric patients with recurrent malignant glioma and diffuse brain stem gliomas. Primary Objectives 1. To estimate the rates of sustained objective response observed prior to disease progression during the first year of treatment with i.v. bevacizumab plus irinotecan given every two weeks in patients with recurrent/progressive/refractory malignant gkioma (Stratum A) and intrinsic brain-stem gliomas (Stratm B) 2.To document changes in MR perfusion and diffusion scans obtained within 24-28 hours following the 2nd dose of bevacizumab as compared to baseline and correlate with response. Secondary Objectives 3. To estimate the rate of treatment-related toxicity with i.v. bevacizumab + irinotecan given every two weeks in patients with recurrent/progressive/refractory malignant glioma (HGG) and intrinsic brain-stem gliomas (BSG)4. To estimate the cumulative incidence of sustained objective responses as a function of courses treatment with i.v. bevacizumab plus irinotecan given every two weeks for up to two years in patients with recurrent/progressive/refractory malignant glioma (Stratum A) and intrinsic brain-stem gliomas (Stratum B). 5. To estimate the distributions of survival and event-free survival (EFS) for two years following initiation of protocol treatment in patients with recurrent/progressive/refractory HGG and BSG. 6. To correlate functional changes in tumor with responses to treatment with bevacizumab + irinotecan using MR perfusion/diffusion imaging, and Fluorodeoxyglucose (FDG) positron emission tomography (PET). 7. To obtain serum pharmacokinetics of bevacizumab in children with HGG or BSG. 8. To estimate vascular endothelial growth factor receptor-2 (VEGF-R2) expression in peripheral blood mononuclear cells (PBMC) prior to treatment and its downregulation following two doses of single-agent bevacizumab and correlate this finding with permeability changes in the tumor on MR perfusion imaging obtained 24-48 hours following the 2nd dose bevacizumab. The prognosis of patients with recurrent high-grade glioma and diffuse brain stem glioma is poor and treatment failure is frequently mediated by drug resistance. Novel strategies are required for improving outcome for these patients. Tumor angiogenesis plays a major role in tumor growth,invasion, and metastasis. Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis and is widely expressed in brain tumors especially malignant glioma. Bevazizumab is a humanized monoclonalantibody that is a pecific inhibitor of VEGF and has been shown in pre-clinical and clinical studies to be safe and useful in controlling tumor growth by itself or in combinationwith standard chemotherapy. The combination of Bevacizumab plus chemotherapy is expected to have a synergistic effect in tumor control. Randomized phase III studies have demonstrated that such a combination improves tumor response rates and survival.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 贝伐单抗与伊立康（Irinotecan）（CPT-11）结合使用良好，并表现出复发性恶性神经胶质瘤和弥漫性脑干神经胶质瘤的小儿患者的客观肿瘤反应。 主要目标 1。估计在疾病进展前观察到的持续客观反应的速率。 Bevacizumab Plus Irinotecan每两周接受一次复发/进行/进行性/难治性恶性GKIoma（A层）和固有的脑干神经胶质瘤（Stratm b）2的患者2.在24-28小时内进行了24-28小时的变化，在24-28小时内获得了与贝氏剂量相比，与基线相比，在24-28小时内获得。 次要目标3。估计与静脉注射的治疗相关毒性率复发/进行/进行性/难治性恶性神经胶质瘤（HGG）和内在的脑茎神经胶质瘤（BSG）患者（BSG）4。估计持续客观响应的累积发生率是静脉注射课程治疗的函数。复发性/进行/进行性/难治性恶性神经胶质瘤（地层A）和内在的脑茎神经胶质瘤（B）患者（bevacizumab Plus Irinotecan每两周一次，每两周一次，持续两年。 5。估计在复发/进行/进行性/难治性HGG和BSG患者的协议治疗开始后两年内生存和无事件生存期（EFS）的分布。 6。使用MR灌注/扩散成像以及氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）将肿瘤的功能变化与对贝伐单抗 +虹膜治疗的反应相关。 7。在患有HGG或BSG的儿童中获得贝伐单抗的血清药代动力学。 8。在治疗前估计外周血单核细胞（PBMC）中血管内皮生长因子2（VEGF-R2）表达，及其在两剂单剂量的贝伐单抗后的下调，并将这种发现与MR灌注成像中24-48小时的肿瘤变化的发现与肿瘤变化相关。 复发性高度神经胶质瘤和弥漫性脑干神经胶质瘤患者的预后较差，并且治疗失败经常通过耐药性介导。 需要新的策略来改善这些患者的预后。 肿瘤血管生成在肿瘤生长，侵袭和转移中起主要作用。 血管内皮生长因子（VEGF）是血管生成的主要介体，在脑肿瘤，尤其是恶性神经胶质瘤中广泛表达。 Bevazizumab是一种人源化的单克隆抗体，是VEGF的特定抑制剂，在临床前和临床研究中已显示出可用于自身或在标准化学疗法联合使用的肿瘤生长方面安全可用。 贝伐单抗加化学疗法的结合预计将在肿瘤控制中具有协同作用。 随机III期研究表明，这种组合可以提高肿瘤反应率和存活率。