CLINICAL TRIAL: PHASE II TRIAL OF PIRFENIDONE IN CHILDREN, ADOLESCENTS, AND YOUN

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。 摘要 吡非尼酮是一种新的实验药物，已被发现对治疗各种纤维化(疤痕)情况有效。吡非尼酮针对的生长因子与丛状神经纤维瘤中也存在的生长因子相同。预计吡非尼酮将为NF1患者提供一种控制肿瘤的手段。 具体目标 主要目标 1.确定1型神经纤维瘤病(NF1)和无法手术的症状性丛状神经纤维瘤的儿童和年轻人长期口服吡非尼酮的最大耐受量(28天周期，周期之间没有休息时间)。 2.明确NF1相关丛状神经纤维瘤患者对吡非尼酮的客观有效率。 3.描述和确定长期口服吡非尼酮(28天周期，周期之间没有休息期)对患有NF1的儿童和年轻人的毒性。 次要目标 1.使用美国国立卫生研究院(NIH)儿科疾病影响(IPI)量表评估接受吡非尼酮治疗的患者的生活质量，该量表评估疾病和治疗对儿童行为的影响，并评估这一新评估工具衡量儿童生活质量变化的能力。 2.评价三维磁共振成像(3D-MRI)在丛状神经纤维瘤诊断中的价值，并与常规二维MRI(2-DMRI)和一维MRI(1-D-MRI)数据分析进行比较。 3.将因临床原因接受肿瘤手术或活组织检查的患者的肿瘤标本捐赠给密苏里州圣路易斯市华盛顿大学现有的组织库。丛状神经纤维瘤的肿瘤标本将接受中央病理检查，包括详细的形态、超微结构免疫组织化学和mRNA基因表达谱分析。 4.在获得IRB批准后，将在本次试验中获得的肿瘤标本提供给科学界，以收集更多关于丛状神经纤维瘤的病理、遗传学和细胞生物学的信息。

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. ABSTRACT Pirfenidone is a new experimental drug that has been found to be effective in treating a variety of fibrosing (scarring) conditions. Pirfenidone targets the same growth factors that are also present in plexiform neurofibromas. it is expected that pirfenidone will provide a means of controlling tumors inpatients with NF1. SPECIFIC AIMS Primary Objectives 1. To determine the maximum tolerated of pirfenidone administered on a chronic oral schedule (28 day cycles with no rest period between cycles) in children and young adults with neurofibromatosis type 1 (NF1) and inoperable, symptomatic plexiform neurofibromas. 2. To define the objective response rate to pirfenidone in NF1-related plexiform neurofibromas. 3. To describe and define the toxicities of pirfenidone, administered on a chronic oral schedule (28 day cycles with no rest period between cycles), in children and young adults with NF1. Secondary Objectives 1. To assess the quality of life of patients treated with pirfenidone using the National Institutes of Health (NIH) Impact of Pediatric Illness (IPI) Scale, which assesses the impact of disease and treatment on children's behavior, and to evaluate the ability of this new assessment tool to measure changes in a cihild's quality of life. 2. To assess the value of three-dimensional MRI (3-D MRI) in the evaluation of plexiform neurofibromas, and to compare 3-D MRI to conventional two-dimensional MRI (2-DMRI) and one - dimensional MRI (1-D-MRI) data analysis. 3. To contribute tumor specimens from patients who undergo tumor surgery or biopsies for clinical reasons to an already-existing tissue bank at Washington University, St. Louis, MO. Tumor specimens of plexiform neurofibromas will undergo central pathology review, including detailed morphological, ultrastructural immunohistochemical, and MRNA gene expression profile analysis. 4. To make tumor specimens that are obtained on this trial available to the scientific community, after obtaining IRB approval, in order to collect more information on the pathology, genetics, and cellbiology of plexiform neurofibromas.