PEDIATRIC ONCOLOGY GROUP - PHASE I TRIALS IN CHILDREN

儿科肿瘤学组 - 儿童 I 期试验

• 批准号: 3549907
• 负责人: TERESA J. VIETTI
• 金额: $ 35.14万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3549907
• 关键词: 6 thioguanine; adolescence (12-20); antineoplastics; bioassay; biological response modifiers; biotransformation; cell mediated lymphocytolysis test; cell population study; child (0-11); cis platinum compound; clearance rate; clinical trials; colony stimulating factor; cooperative study; deferoxamine; dosage; drug adverse effect; drug metabolism; drug resistance; drug screening /evaluation; etoposide; excretion; flow cytometry; high performance liquid chromatography; human subject; human therapy evaluation; immunocytochemistry; longitudinal human study; lymphocyte proliferation; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; neuroblastoma; pediatric neoplasm /cancer; pharmacokinetics; therapy compliance; ultraviolet spectrometry

The POG wishes to continue timely performance of phase I studies of new cytotoxic, biologic, and maturational agents in children with advanced disease resistant to standard therapy. The MTD achieved and the associated toxicities will determine the dose, supportive care and precautions to be used in phase II trials in children. Pharmacokinetic and pharmacodynamic studies will be done on children at the starting dose, when there is evidence of a biologic effect and at the MTD. Biological assays will be obtained if a biological response modifier or maturational agent is under investigation. The starting dose level will be determined after consultation with the CTEP drug monitor. If the starting dose is 80% of the MTD in adults, the subsequent escalation of doses will be 20%. If phase I studies have not been done in adults then the starting dose will be 1/10 of the LD10 in mice (or 1/3 of the TDL in large animals) and a modified Fibonacci scheme will be used for dose escalation. Investigators will submit all data forms at weekly intervals to the Study Chairman and the Scientific Administrator. The Study Chairman and the CTEP drug monitor will be notified by telephone of any unusual, unexpected, unacceptable, previously unreported toxicity, or death on study. Every three months the Study Chairman will prepare a summary of the patients entered at each dose level, the toxicity observed, and the pharmacologic data for biologic studies obtained and send a copy to the Phase I Subcommittee Chairman and the Scientific Administrator. The Phase I Subcommittee Chairman will review these and submit them to the Phase I Chairman and the CTEP. Every six months, compliance to protocol requirements and timeliness of data submission will be reviewed by the Phase I Compliance Committee. Six months after the last patient entry, a manuscript will be prepared and submitted to the Writing Committee. All institutions entering patients on protocol will be audited at least once every three years.

POG希望继续及时进行新的新研究 晚期儿童的细胞毒性，生物学和成熟剂 抗标准治疗的疾病。 MTD达到的和相关的 毒性将决定剂量，支持性护理和预防措施 在儿童的II期试验中使用。 药代动力学和药效学 在开始时，将对儿童进行研究 生物学作用和MTD的证据。 生物测定将是 如果生物反应修饰剂或成熟剂处于 调查。 起始剂量水平将在 与CTEP药物监测仪协商。 如果起始剂量是80％ 成人的MTD随后的剂量升级将为20％。 如果 第一阶段研究尚未在成年人中进行，因此起始剂量将是 小鼠（大动物中TDL的1/3）的LD10的1/10和A 修改后的斐波那契方案将用于剂量升级。 调查人员 将以每周间隔提交所有数据表格，并将 科学管理员。 研究主席和CTEP药物显示器 电话将通过电话通知任何不寻常的，出乎意料的，不可接受的， 以前未报告的毒性或研究死亡。 每三个月 学习主席将准备每次剂量输入的患者的摘要 水平，观察到的毒性和生物学的药理学数据 获得的研究并将副本发送到第一阶段小组委员会主席和 科学管理员。 第一阶段小组委员会主席将 查看这些并将其提交给第一阶段主席和CTEP。 每一个 六个月，遵守协议要求和数据的及时性 提交将由第一阶段合规委员会审查。 六 最后一个患者进入几个月后，将准备手稿， 提交给写作委员会。 所有进入患者的机构 协议将至少每三年进行一次审核。