PHASE IB STUDY TO EVALUATE SAFETY AND TOLERANCE OF REPETITIVE DAILY

IB 期研究评估重复性日常活动的安全性和耐受性

• 批准号: 6274566
• 负责人: JAMES RUFFER
• 金额: $ 2.5万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-15 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6274566
• 关键词: clinical research; clinical trial phase I; combination cancer therapy; drug screening /evaluation; glioblastoma multiforme; human subject; human therapy evaluation; neoplasm /cancer chemotherapy; neoplasm /cancer radiation therapy; oxygen tension; radiosensitizer

RSR13 is a synthetic allosteric modifier of hemoglobin. It decreases the oxygen affinity of hemoglobin and augments oxygen unloading in the microvasculature which increases the oxygen diffusion gradient to the tissues. By increasing tissue oxygenation, RSR13 may reduce tumor hypoxia and enhance the cytotoxic effects of radiation therapy used to treat cancer patients with solid tumors. To test the safety, tolerance, and maximally tolerated repetitive dose of RSR13, we conducted a non- randomized, open-label, multi-center safety study in patients who received a conventional six-week course of cranial radiation therapy for glioblastoma multiforme. Patients enrolled in this study had a histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme). The dose of RSR13 was 100 mg/kg at a concentration of 20 mg/mL, administered over 60 minutes by continuous infusion via a central venous access device. RSR13 administration began on the first day of radiation therapy and was given so that the end of the infusion occured within 30 minutes prior to the start of radiation therapy. Two dose frequency groups, Groups A and B, with nine patients per group, were used. Patients in Group A received 100 mg/kg RSR13 every other day of radiation therapy, and patients in Group B received 100 mg/kg RSR13 every day of radiation therapy.

RSR 13是血红蛋白的合成变构修饰剂。 它减少 血红蛋白的氧亲和力，并增加氧卸载在 微血管系统，其增加了氧扩散梯度， 组织中 通过增加组织氧合，RSR 13可以减少肿瘤细胞的生长。 缺氧和增强放射治疗的细胞毒性作用， 治疗患有实体瘤的癌症患者。为了测试安全性，耐受性， 和最大耐受重复剂量的RSR 13，我们进行了一个非- 一项随机、开放标签、多中心安全性研究， 接受了为期六周的常规颅脑放射治疗， 多形性胶质母细胞瘤 入组本研究的患者 组织学证实幕上IV级星形细胞瘤 （多形性胶质母细胞瘤）。 RSR 13的剂量为100 mg/kg， 浓度为20 mg/mL，在60分钟内通过连续给药 通过中心静脉接入装置进行输注。 开始RSR 13给药 在放射治疗的第一天， 输注发生在放射开始前30分钟内 疗法 两个剂量频率组，A组和B组，9例患者 每一组，都被使用。 A组患者接受100 mg/kg RSR 13 放疗隔日一次，B组患者接受放疗 100 mg/kg RSR 13每天的放射治疗。