PEDIATRIC ONCOLOGY GROUP - PHASE I TRIALS IN CHILDREN

儿科肿瘤学组 - 儿童 I 期试验

• 批准号: 3549908
• 负责人: TERESA J. VIETTI
• 金额: $ 36.38万
• 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/3549908
• 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 I 期研究 晚期儿童的细胞毒性剂、生物剂和成熟剂 对标准治疗有抵抗力的疾病。 达到的 MTD 以及相关的 毒性将决定剂量、支持治疗和预防措施 用于儿童的 II 期试验。 药代动力学和药效学 研究将以起始剂量对儿童进行，当有 生物效应和 MTD 的证据。 生物检测将 如果生物反应调节剂或成熟剂处于以下状态，则获得 调查。 起始剂量水平将在之后确定 咨询 CTEP 药物监测员。 如果起始剂量是 80% 根据成人的 MTD，后续剂量将增加 20%。 如果 尚未在成人中进行 I 期研究，因此起始剂量为 小鼠 LD10 的 1/10（或大型动物 TDL 的 1/3）和 修改后的斐波那契方案将用于剂量递增。 调查员 将每周向研究主席提交所有数据表格，并且 科学管理员。 研究主席和 CTEP 药物监测员 将通过电话通知任何异常、意外、不可接受的情况， 先前未报告的毒性或研究中的死亡。 每三个月 研究主席将准备一份每次剂量参与患者的总结 水平、观察到的毒性以及生物制剂的药理学数据 获得的研究并将副本发送给第一阶段小组委员会主席，以及 科学管理员。 第一阶段小组委员会主席将 审查这些内容并将其提交给第一阶段主席和 CTEP。 每一个 六个月，符合协议要求和数据的及时性 提交的内容将由第一阶段合规委员会进行审查。 六 最后一位患者录入后几个月，将准备一份手稿并 提交给写作委员会。 所有机构均在 协议将至少每三年审核一次。