MULTIPLE DOSE STUDY OF SAFETY OF ABT 627

ABT 627 安全性的多剂量研究

• 批准号: 6114368
• 负责人: Michael A Carducci
• 金额: $ 2.06万
• 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/6114368
• 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 Of the 19 patients, 4 remain on study, 2 were withdrawn early, 4 patients progressed after 28 days of therapy, and 9 patients received therapy on the extension trial.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.

该 I 期临床试验旨在测试安全性、耐受性和 ABT-627 对于晚期前列腺癌患者的药代动力学 (PCA) 和其他难治性腺癌于 7 月开始接受治疗 1997.评估肿瘤反应和肿瘤标志物的变化。 这 是一项连续 28 天每天口服 ABT-627 的剂量递增研究， 接下来是一周的休息时间。 如果有临床益处的证据， 患者可以继续接受 ABT-627 治疗。 十九名患者 已入组 6 个剂量水平（10、20、30、45、60、75 毫克/天）。 该队列（18 名男性，1 名女性）由 14 名 PCA 患者、2 名 肾细胞癌 2 例，结肠癌 2 例，肺癌 1 例。 两名患者因继发于早期退出而无法进行评估 通过脊髓受压证明疾病进展。 毒性已 最小，一名患者出现短暂的 2 级头痛 20 毫克/天，另一名患者出现 3 级头痛，持续 4-5 天。 鼻塞是最常见的症状。 无血液学、 在接受治疗的患者中已发现肝脏或肾脏毒性。 早期药代动力学与健康人获得的一致 志愿者。 该药剂的半衰期接近 25 小时。 三 需要镇痛的麻醉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 研究期间，剂量水平为 10、20、30 毫克/天）。 其中一名患者 小队列的 PSA 下降 < 50%，其余 PCA 患者 PSA 稳定或小幅下降。 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 年后病情进展 治疗天数，9 名患者在扩展试验中接受了治疗。 应计项目继续进展顺利。总而言之，ABT-627，一个 ETA 内皮素受体拮抗剂，对于患有以下疾病的患者具有良好的耐受性 晚期腺癌。 患者的早期 PSA 反应 前列腺癌和骨痛的改善以及随之而来的减少 麻醉药品的使用令人鼓舞。 该药物的 II 期研究是 该机构和全国其他中心正在进行 国际上。 此次一期试验奠定了基础 加速药物开发计划。