ADVL0311, A PHASE I STUDY OF PEMETREXED (LY231514, ALIMTA) (NSC #698037, IND

ADVL0311，培美曲塞（LY231514，ALIMTA）的 I 期研究（NSC

• 批准号: 7374983
• 负责人: SUSAN M. BLANEY
• 金额: $ 1.15万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7374983
• 关键词: ADVL0311; PHASE; STUDY; PEMETREXED; LY231514

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. This is a phase I study of pemetrexed (LY231514, Alimta) in children and adolescents with recurrent solid tumors. Pemetrexed is a novel antifolate that inhibits multiple targets. Antimetabolites are cytotoxic drugs structurally similar to naturally occurring molecules necessary for the synthesis of pyrimidines, purines, and nucleic acids. Pemetrexed has anti-tumor activity through inhibition of several key folate-requiring enzymes, including thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyl transferase (GARFT). Pediatric and adolescent patients with recurrent solid tumors will be eligible for study if they have adequate hematologic, hepatic, renal, and pulmonary status. Informed consent will be required. Participants will be given pemetrexed as a 10 minute IV infusion every 21 days. The starting dose will be 400 mg/m 2, and subsequent levels will be 30% higher. Pharmacokinetics and pharmacogenetics studies will be performed. Other correlative studies include a preliminary assessment of the correlation of the expression of TS, DHFR, GARFT, reduced folate carrier (RFC), folylpolyglutamate synthetase (FPGS) and gamma glutamyl hydrolase (GGH) as well as methylthioadenosine phosphorylase (MTAP) deletion with pemetrexed response, as is possible within the confines of a Phase I trial.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。这是一项针对患有复发性实体瘤的儿童和青少年的培美曲塞（LY231514，Alimta）的 I 期研究。培美曲塞是一种新型抗叶酸药，可抑制多个靶点。抗代谢物是细胞毒性药物，其结构类似于合成嘧啶、嘌呤和核酸所需的天然分子。培美曲塞通过抑制几种关键的叶酸需求酶而具有抗肿瘤活性，包括胸苷酸合成酶 (TS)、二氢叶酸还原酶 (DHFR) 和甘氨酰胺核糖核苷酸甲酰基转移酶 (GARFT)。患有复发性实体瘤的儿童和青少年患者如果具有足够的血液学、肝脏、肾脏和肺部状况，将有资格参加研究。需要知情同意。 参与者将每 21 天接受一次 10 分钟静脉输注培美曲塞。起始剂量为 400 mg/m 2 ，后续剂量将增加 30%。将进行药代动力学和药物遗传学研究。其他相关研究包括初步评估 TS、DHFR、GARFT、还原叶酸载体 (RFC)、叶酰聚谷氨酸合成酶 (FPGS) 和 γ 谷氨酰水解酶 (GGH) 以及甲硫腺苷磷酸化酶 (MTAP) 缺失与培美曲塞反应之间的相关性，这在有限的范围内是可能的。 第一阶段试验。