STUDY OF 90 YTTRIUM/DOTA/BIOTIN LOCALIZATION IN ADVANCED CANCER

90 钇/DOTA/生物素在晚期癌症中定位的研究

• 批准号: 6246163
• 负责人: Susan J. Knox
• 金额: $ 3.61万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-15 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6246163
• 关键词: adenocarcinoma; binding proteins; biotin; clinical research; combination cancer therapy; dosage; drug screening /evaluation; enzyme linked immunosorbent assay; human subject; human therapy evaluation; immunoconjugates; monoclonal antibody; neoplasm /cancer immunotherapy; neoplasm /cancer pharmacology; neoplasm /cancer radionuclide therapy; pharmacokinetics; whole body radionuclide scanning; yttrium

In this study, patients with advanced adenocarcinoma that reacts with NR-LU-10 monoclonal antibody will be treated with radioimmunotherapy using a pretargeting approach. Using this method, each patient will receive a total of three infusions. The first infusion will consist of NR-LU-10 monoclonal antibody/Streptavidin, followed by a clearing agent (Galactose-Biotin-Human Serum Albumin) to remove circulating unbound antibody, and lastly, 111In and 90Y-DOTA-Biotin. Patients will then be imaged in the anterior and posterior projections in a whole body mode immediately following injection and at three hours and one, two, and five days following treatment. Dosed to tumor and normal tissue will be calculated from data obtained from the immunoscintigraphy studies as well as tumor and bone marrow biopsies in a subset of patients. A minimum of three patients will be treated at each dose level until the maximal tolerated dose is established. Tumor size measurements will be obtained whenever possible. Clinical efficacy will be assessed using a variety of imaging studies appropriate for the particular patients known/monitored sites of disease, as well as by serum tumor marker measurements when indicated. In addition, the incidence and timing of human anti-immunoconjugate antibody responses will be determined by ELISA assays. Pharmacokinetic profiles will be determined by measuring the levels of immunoconjugate in serum either by ELISA or RIA assays. The primary objectives of the study are to establish the MTD of 90Y- Biotin-DOTA when administered as part of a pretargeting approach to evaluate the safety of the pretargeting approach. To date 13 patients have been treated on this study at dose levels ranging from 50mCi/m2 to 90mCi/m2. At the higher doses there have been site dependent reductions in tumor size in some of the patients, but none of the patients have had a PR or CR. The only significant toxicities noted to date are reversible myelosuppression and transient gastrointestinal side effects, neither of which has been dose limiting. Dose escalation will continue as described in the protocol until the MTD is determined.

在这项研究中，晚期腺癌患者， NR-LU-10单克隆抗体将接受放射免疫治疗 使用预先瞄准的方法。 使用这种方法，每个患者都可以 共输注三次。 首次输注将包括 NR-LU-10单克隆抗体/链霉抗生物素蛋白，然后是清除剂 （半乳糖-生物素-人血清白蛋白），以清除循环中未结合的 抗体，最后是111 In和90 Y-DOTA-生物素。 患者将在 以全身模式在前后投影中成像 注射后立即和3小时以及1、2和 治疗后5天。 对肿瘤和正常组织的剂量将是 根据免疫闪烁成像研究获得的数据计算， 以及一部分患者的肿瘤和骨髓活检。 一 每个剂量水平至少治疗3例患者，直至 确定最大耐受剂量。 肿瘤大小测量将 只要有可能就能得到。 临床疗效将使用 适合特定患者的各种影像学检查 已知/监测的疾病部位以及血清肿瘤标志物 如有指示，测量。 此外， 人抗免疫偶联物抗体应答将通过 ELISA测定。 药代动力学特征将通过测量 通过ELISA或RIA测定血清中免疫缀合物的水平。 本研究的主要目的是确定90 Y的MTD- 生物素-DOTA作为预靶向方法的一部分， 评估预靶向方法的安全性。 迄今为止，13名患者 在本研究中接受治疗的剂量水平范围为50 mCi/m2至 90 mCi/m2。 在较高剂量下， 一些患者的肿瘤大小减少，但没有一个患者 患者获得PR或CR。 注意到的唯一显著毒性是 数据为可逆性骨髓抑制和一过性胃肠道副作用 影响，两者都不是剂量限制。 剂量递增将 继续按照方案中的描述，直至确定MTD。