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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 摘要 吡非尼酮是一种新的实验性药物，已被发现可有效治疗各种纤维化（瘢痕）状况。 吡非尼酮靶向的生长因子与丛状神经纤维瘤中存在的生长因子相同。 预期吡非尼酮将提供控制患有NF 1的住院患者的肿瘤的手段。 具体目标 主要目标 1. 在患有1型神经纤维瘤病（NF 1）和无法手术的症状性丛状神经纤维瘤的儿童和年轻成人中，确定吡非尼酮长期口服方案（28天为一个周期，周期之间无停药期）的最大耐受性。 2. 确定吡非尼酮治疗NF 1相关丛状神经纤维瘤的客观缓解率。 3. 描述和定义在NF 1儿童和年轻成人中以长期口服方案（28天为一个周期，周期之间无休息期）给予吡非尼酮的毒性。 次要目的 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，并评价这种新评估工具测量儿童生活质量变化的能力。 2. 探讨三维MRI（3-D MRI）对丛状神经纤维瘤的诊断价值，并与常规二维MRI（2-DMRI）和一维MRI（1-D-MRI）进行数据分析比较。 3. 将因临床原因接受肿瘤手术或活检的患者的肿瘤标本捐献给位于密苏里州圣路易斯市华盛顿大学的现有组织库。 丛状神经纤维瘤的肿瘤标本将接受中心病理学审查，包括详细的形态学、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，将本试验中获得的肿瘤标本提供给科学界，以收集有关丛状神经纤维瘤的病理学、遗传学和细胞生物学的更多信息。

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.