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

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

• 批准号: 8356679
• 负责人: SUSAN M. BLANEY
• 金额: $ 0.91万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8356679
• 关键词: Brain Neoplasms; Brain Stem Glioma; Child; Childhood; Clinical Research; Clinical Trials; Diffuse; Diffusion; Disease Progression; Disease-Free Survival; Dose; Down-Regulation; Drug Kinetics; Drug resistance; Funding; Glioma; Grant; Hour; Image; Incidence; Malignant Glioma; Mediating; Mediator of activation protein; National Center for Research Resources; Neoplasm Metastasis; Outcome; Patients; Perfusion; Peripheral Blood Mononuclear Cell; Permeability; Play; Principal Investigator; Randomized; Recurrence; Refractory; Research; Research Infrastructure; 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; cost; fluorodeoxyglucose positron emission tomography; improved; inhibitor/antagonist; irinotecan; novel strategies; outcome forecast; phase 2 study; 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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT HYPOTHESIS 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. SPECIFIC AIMS 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 glioma (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. BACKGROUND AND SIGNIFICANCE 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.

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