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 Of the 19 patients, 4 remain on study, 2 were withdrawn early, 4 patients progressed after 28 days of therapy, and 9 patients received therapy on the extension trial.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安全性、耐受性和 ABT-627在晚期前列腺癌患者中的药代动力学 (PCa)和其他难治性腺癌7月份开始增加 1997年。评估肿瘤反应和肿瘤标志物的变化。这 是ABT-627的剂量递增研究，每天口服，持续28天， 之后是一周的休息。如果有临床益处的证据， 患者可以继续接受ABT-627治疗。19名患者 已经登记了6个剂量水平(10，20，30，45，60，75毫克/天)。 队列(男18例，女1例)包括14例前列腺癌患者，2例 肾细胞癌，2例结肠癌，1例肺癌。 两名患者因早期停药继发于 疾病进展表现为脐带受压。毒性已经被 轻微，有一名患者出现短暂的2级头痛 20毫克/天，另一名3级头痛患者持续4-5天。 鼻塞是最常见的主诉。没有血液学检查， 在接受治疗的患者中，已经注意到了肝脏或肾脏的毒性。 早期药代动力学结果与健康人的结果一致 志愿者。该制剂的半衰期接近25小时。三 需要疼痛的麻醉剂患者的疼痛得到改善 疼痛等级降低或麻醉剂使用减少(剂量 每天10、20、30毫克)。这里有一位病人 小队列的PSA下降了50%，其余的PCa患者 PSA稳定或略有下降。在19名患者中，有4名 仍在研究中，2名患者提前退出，4名患者在28岁后进展 治疗天数，9名患者在延长试验中接受治疗。 应计利润继续走得非常好。总而言之，ABT-627，一架埃塔 内皮素受体拮抗剂，耐受性良好 晚期腺癌。慢性前列腺炎患者的早期PSA反应 前列腺癌与骨痛的改善和伴随的减少 在麻醉药品的使用方面是令人鼓舞的。该药的第二阶段研究是 在这个机构和全国其他中心正在进行 在国际上。这一阶段的试验为此奠定了基础 加快药品开发规划。