MULTIPLE DOSE STUDY OF SAFETY OF ABT 627

ABT 627 安全性的多剂量研究

• 批准号: 6297549
• 负责人: Michael A Carducci
• 金额: $ 0.23万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6297549
• 关键词: adenocarcinoma; antineoplastics; clinical research; clinical trial phase I; colon neoplasms; dosage; drug administration rate /duration; drug adverse effect; drug screening /evaluation; human subject; lung neoplasms; neoplasm /cancer chemotherapy; neoplasm /cancer classification /staging; oral administration; pharmacokinetics; prostate neoplasms; renal cell carcinoma

This Phase I clinical trial to test the safety, tolerability, and pharmacokinetics of ABT-627 for patients with advanced prostate cancer (PCA) and other refractory adenocarcinomas opened to accrual in July 1997. Tumor response and changes in tumor markers are evaluated. This is a dose escalation study of ABT-627 given orally each day for 28 days, followed by a week break. If there is evidence of clinical benefit, patients may continue to receive ABT-627 therapy. Nineteen patients have been enrolled across 6 dose levels (10,20,30,45,60, 75 mg/day). The cohort (18 males, 1 female) is made up of 14 patients with PCA, 2 with renal cell cancer, 2 with colon cancer, and 1 with lung cancer. Two patients are not evaluable because of early withdrawal secondary to disease progression as evidenced by cord compression. Toxicity has been minimal, with one patient experiencing a short-lived Grade 2 headache at 20 mg/day and one other patient with a Grade 3 headache for 4-5 days. Nasal congestion is the most frequent complaint. No hematologic, hepatic, or renal toxicity has been noted in the treated patients. Early pharmacokinetics are consistent with those obtained from healthy volunteers. The agent has a half-life of nearly 25 hours. Three patients with narcotic requiring pain had improvement in their pain with either a reduction in pain ratings or a decrease in narcotic use (Dose levels 10, 20, 30 mg/day) during the study period. One patient in this small cohort had a PSA decline < 50%, with the remaining PCA patients having PSA stabilization or minor declines. Of the 19 patients, 4 remain on study, 2 were withdrawn early, 4 patients progressed after 28 days of therapy, and 9 patients received therapy on the extension trial. Accrual continues to go exceedingly well. In summary, ABT-627, an ETA endothelin-receptor antagonist, is well tolerated in patients with advanced adenocarcinoma. Early PSA responses in the patients with prostate cancer and improvement in bone pain with a concomitant decrease in narcotic use is encouraging. Phase II studies with this agent are underway at this institution and other centers nationally and internationally. This Phase I trial laid the foundation for this accelerated program of drug development.

这项I期临床试验旨在测试其安全性、耐受性和 ABT-627治疗晚期前列腺癌的药代动力学 (PCA)和其他难治性腺癌在7月开始增加 1997. 评价肿瘤反应和肿瘤标志物的变化。 这 是一项ABT-627每日口服给药28天的剂量递增研究， 然后休息一周 如果有临床获益的证据， 患者可以继续接受ABT-627治疗。 19名患者 在6个剂量水平（10、20、30、45、60、75 mg/天）下入组。 该队列（18名男性，1名女性）由14名PCA患者组成，2名 肾细胞癌，2例结肠癌，1例肺癌。 2例患者由于继发于以下原因而提前退出，因此无法评价 脊髓压迫所证实的疾病进展。 毒性已 极轻微，1例患者出现短暂的2级头痛 20 mg/天，另一名患者3级头痛4-5天。 鼻塞是最常见的主诉。 没有血液学检查 肝或肾毒性。 早期药代动力学与从健康人中获得的结果一致。 志愿者 该药剂的半衰期接近25小时。 三 需要麻醉剂疼痛的患者的疼痛有所改善， 疼痛评分降低或麻醉剂使用减少（剂量 水平10、20、30 mg/天）。 一个病人 小队列PSA下降<50%，其余PCA患者 PSA稳定或轻微下降。 19名患者中，4名 继续研究，2例患者提前退出，4例患者在28小时后进展 天的治疗，和9名患者接受治疗的扩展试验。 应计利润继续非常好。总之，ABT-627，一种ETA 内皮素受体拮抗剂，在以下患者中耐受良好： 晚期腺癌 前列腺癌患者的早期PSA应答 前列腺癌和骨痛改善，同时减少 麻醉品的使用令人鼓舞。 该药物的II期研究是 在这个机构和全国其他中心进行， 化国际大 第一阶段试验为此奠定了基础 加速药物开发计划。