PEDIATRIC BRAIN TUMOR CONSORTIUM--CHOP MEMBERSHIP

这项提案的总体目标是改善儿童原发性脑肿瘤的治疗结果。这将通过由新成立的儿科脑瘤临床试验联盟(PBTC)对前景看好的新药、给药技术、生物疗法和放射治疗策略进行的第一阶段和第二阶段临床评估来实现。该联盟将把8家优秀医疗机构的经验和资源整合到一个组织结构中，旨在促进对儿童脑瘤新疗法的快速和成功研究。第二个目标是利用联盟机制共享脑瘤标本以及其他临床和实验室数据，并进行与神经成像、药理学和儿童脑肿瘤生物学有关的研究。为了实现这些目标，PBTC必须依靠每个参与机构的特殊优势和资源。因此，我们提出以下具体目标以推进PBTC的目标：目的1.作为成员机构参与PBTC临床试验、实验室和神经影像研究；目的2.开发儿童中枢神经系统肿瘤的新实验疗法，并为PTBC的I/II期临床试验提出这些策略；目的3.建议和促进用于预防或治疗儿童中枢神经系统肿瘤的鞘内疗法的开发和研究；以及目的4.提出和发展局部肿瘤药代动力学和脑肿瘤生物学的神经成像研究，供PBTC成员参与。费城儿童医院(CHOP)拥有：(1)一支由国际公认的儿科神经肿瘤学、放射肿瘤学、神经外科、神经放射学、药理学和新药开发领先者组成的杰出的多学科临床团队；(2)大量儿童原发脑瘤患者可供研究；(3)最先进的诊断和研究设施，用于神经成像(MRI、磁共振波谱、PET、SPECT)、神经外科(计算机图像引导手术)和放射治疗(立体定向放射外科、伽玛刀、近距离放射治疗)；(4)美国国立卫生研究院资助的脑肿瘤银行，存储来自CHOP、纽约大学和贝丝以色列(NYC)的脑瘤活检标本；(5)国际公认的神经病理学专业知识；(6)在生物统计和临床试验数据管理方面的广泛机构资源，以及在临床护理和研究方面的卓越声誉；(7)在组织和协调多机构临床试验方面的经验；以及(8)大量高质量、临床相关、同行评议和NIH资助的脑肿瘤研究。这些方案和体制优势支持了我们具体目标的可行性，符合RFA规定的财团参与标准，并极大地提高了PBTC实现其长期目标的可能性。

The overall objective of this proposal is to improve therapeutic outcomes for children with primary brain tumors. This will be accomplished by Phase I and II clinical evaluations of promising new therapeutic drugs, delivery technologies, biological therapies, and radiation treatment strategies conducted by a newly-established Pediatric Brain Tumor Clinical Trials Consortium (PBTC). This consortium will combine the experience and resources of eight outstanding medical institutions in an organizational structure designed to facilitate a rapid and successful study of new therapies for childhood brain tumors. A second objective is to utilize the consortium mechanism to share brain tumor specimens as well as other clinical and laboratory data and to conduct research pertaining to neuroimaging, pharmacology, and the biology of childhood brain tumors. To achieve these objectives, the PBTC must rely on the special strengths and resources of each participating institution. Accordingly, we propose the following Specific Aims to advance PBTC goals: Aim 1. to participate as a Member Institution in PBTC clinical trials, laboratory, and neuroimaging studies; Aim 2. to develop new experimental therapies for CNS tumors in children and propose these strategies for phase I/II clinical trials by the PTBC; Aim 3. to propose and facilitate the development and study of intrathecal therapies for the prophylaxis or treatment of childhood CNS tumors; and Aim 4. to propose and develop neuroimaging studies of regional tumor pharmacokinetics and brain tumor biology for participation by PBTC members. The Children's Hospital of Philadelphia (CHOP) has: (1) an outstanding multi- disciplinary clinical team of internationally-recognized leaders in pediatric neuro-oncology, radiation oncology, neurosurgery, neuro-radiology, pharmacology, and new drug development; (2) a large number of patients with childhood primary brain tumors available for study; (3) state-of-the-art facilities for diagnostic and research neuroimaging (MRI, MRSpectroscopy, PET, SPECT), neurosurgery (computer image-guided surgery), and radiation therapy (stereotaxic radiosurgery, Gamma Knife, brachytherapy); (4) an NIH-funded brain tumor bank which stores brain tumor biopsies from CHOP, NYU, and Beth Israel (NYC) (5) internationally-recognized expertise in neuro-pathology; (6) extensive institutional resources for biostatistics and clinical trial data management and a reputation for excellence in clinical care and research; (7) experience in the organization and coordination of multi-institutional clinical trials; and (8) a large number of high quality, clinically relevant, peer reviewed and NIH funded brain tumor research studies. These programmatic and institutional strengths support the feasibility of our specific aims, are responsive to the criteria for consortium participation specified by the RFA, and substantially enhance the likelihood that the PBTC will achieve its long-term goals.