MONOCLONAL ANTIBODY 81C6 I 131 METASTATIC TO LEPTOMENINGES

单克隆抗体 81C6 I 131 转移至软脑膜

• 批准号: 6273969
• 负责人: MARK T BROWN
• 金额: $ 2.88万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6273969
• 关键词: brain neoplasms; clinical research; clinical trial phase I; dosage; drug administration routes; drug screening /evaluation; human subject; human therapy evaluation; immunoconjugates; iodine; meningioma; metastasis; monoclonal antibody; neoplasm /cancer immunotherapy; neoplasm /cancer radionuclide therapy; radiation therapy dosage; radionuclides

This protocol contains two active components, each assigned a separate Duke IRB number, and a third component, which has been successfully completed and is now closed. The component which has been completed utilized 131Iodine-labeled 81C6 monoclonal antibody in the treatment of patients with neoplasms metastatic to the leptomeninges. The purpose of this study was to determine the safety and maximum tolerated dose of intrathecal 131I-labeled 81C6 monoclonal antibody in patients with neoplasms metastatic to the leptomeninges. In one part of this protocol, 81C6 IgG monoclonal antibody conjugated to 131I was utilized in the treatment of neoplasms metastatic to the leptomeninges or postoperative tumor cystic cavities communicating with cerebrospinal fluid. It was a phase I dose-escalation study designed to determine the toxicity profile and maximum tolerated isotope dose. The protocol began at 40 mCi 131I and escalated in 20 mCi increments (i.e., 60, 80, 100, etc. mCi) in cohorts of 3-6 patients per dose level until the maximum tolerated dose was reached. Response were assessed secondarily. The maximum tolerated 131I-81C6 dosage for a single intrathecal administration in adult patients was 80 mCi 131I-81C6 (10 mg protein). The dosage limiting toxicity was hematologic toxicity. We treated 31 patients and noted one partial response and disease stabililzation in 13 of 31 patients (42%). This portion of the protocol has been sucessfully completed, and a manuscript describing the results has been published (see attatched copy). One active component of this protocol utilizes 131I-labeled 81C6 monoclonal antibody in the treatment of patients with primary or metastatic malignant brain tumors with surgically created cystic resection cavities. The purpose of this study is to determine the safety and maximum tolerated dose of 131I-labeled 81C6 monoclonal antibody administered into surgically created cystic tumor resection cavities in patients with primary or metastatic malignant brain tumors. The second active component utilizes 131I-labeled 81C6 monoclonal antibody in the treatment of patients with recurrent cystic gliomas. The purpose of this study is to determine the safety and maximum tolerated dose of 131I- labeled 81C6 monoclonal antibody administered into naturally occurring tumor cyst cavities in patients with recurrent cystic gliomas. 81C6 IgG monoclonal antibody conjugated to 131I is utilized in the treatment of patients with recurrent cystic gliomas or patients with primary or metastatic malignant brain tumors with surgically created cystic resection cavities. These are phase I dose-escalation studies designed to determine the toxicity profile and maximum tolerated isotope dosage for each patient population above. The protocol began at 20 mCi 131I and is escalating in 20 mCi increments (i.e.40, 60, 80, 100, etc. mCi) in cohorts of 3-6 patients per dosage level until the maximum tolerated dosage is reached. Response is assessed secondarily. These studies are continuing to accrue patients. We have identified the maximum tolerated dose as 100 mCi 131I-81C6 (20 mg protein) in previously radiated patients with surgically created cystic resection cavities. This arm of the protocol has closed and a manuscript is in preparation. The other arms of the active protocol components remain open for accrual. These disease entities are all devastating, incurable neurologic complications of cancer where present treatments are inadequate. The development of monoclonal antibodies has provided the potential for more specific therapy of tumors which are reactive with the monoclonal antibody or antibody fragment. Antibodies that are specific to the tumor cells and that do not react with normal brain or spinal cord can be conjugated with therapeutic radioisotopes, such as 131I. This conjugate can then be delivered intrathecally for leptomentingeal neoplasms, into a naturally-ocurring tumor cyst cavity for cystic brain tumors, or into a surgically-created resection cavity for solid brain tumors to deliver a therapeutic dose of radiation with relative specificity for the tumor cells. Radiolabeled monoclonal antibodies may be a significant new therapeutic modality for these disease entities. These are the first studies in the United States to test such compartmental therapy of leptomeningeal neoplasms and brain tumor resection cavities with radiolabeled monoclonal antibodies.

该协议包含两个活动组件，每个组件都分配了一个单独的 Duke IRB编号，以及第三个组件，已成功 已完成，现已关闭。已完成的组件 应用~(131)I标记的81C6单抗治疗卵巢癌 肿瘤转移至软脑膜的患者。目的 本研究旨在确定阿司匹林的安全性和最大耐受量 鞘内~(131)I标记的81C6单抗在慢性病患者中的应用 转移到软脑膜的肿瘤。在这其中的一部分 方案中，结合~(131)I的81C6单抗用于 软脑膜转移性肿瘤的治疗 术后与脑脊液相通的肿瘤囊性腔 流体。这是一项I期剂量递增研究，旨在确定 毒性分布和最大耐受同位素剂量。礼仪开始了 40 MCI 131I，并以20 MCI增量(即60、80、100等)升级 MCI)，每个剂量水平3-6名患者，直到最大耐受量 达到了剂量。对疗效进行二次评定。最大值 单次鞘内给药的131I-81C6耐受量 成人患者为80MCI 131I-81C6(蛋白质10 mg)。剂量限制 毒性为血液学毒性。我们治疗了31名患者，并注意到一名 31例患者中13例部分缓解和病情稳定 (42%)。议定书的这一部分已经成功完成，并且 描述结果的手稿已经出版(见附文 副本)。该协议的一个有源组件利用131I标记的81C6 单抗在治疗原发卵巢癌中的应用 手术造成囊性切除的转移性恶性脑肿瘤 龋齿。本研究的目的是确定其安全性和安全性 ~(131)I标记81C6单抗的最大耐受量 在手术产生的囊性肿瘤切除腔内注射 原发或转移性恶性脑肿瘤患者。这个 第二活性成分利用~(131)I标记的81C6单抗 复发性囊性胶质瘤的治疗。目的 本研究旨在确定~(131)I-的安全性和最大耐受量。 标记81C6单抗注射入自然发生 复发性囊性胶质瘤患者的肿瘤囊腔。81C6免疫球蛋白 ~(131)I标记的单抗用于治疗恶性黑素瘤 复发性囊性胶质瘤患者或原发或 手术造成囊性切除的转移性恶性脑肿瘤 龋齿。这些是I期剂量递增研究，旨在确定 每个患者的毒性分布和最大耐受同位素剂量 人口在以上。该协议开始于20MCI 131I，并在 3-6个队列中的20个MCI增量(即40、60、80、100等) 每个剂量水平的患者，直到达到最大耐受剂量。 其次是对反应进行评估。这些研究正在继续积累。 病人。我们已确定最大耐受量为100毫升。 ~(131)I-81C6(20 mg蛋白质)在既往放射治疗患者中的应用 形成了囊性切除空洞。协议的这条手臂已经关闭 一份手稿正在准备中。现行协议的其他武器 组件仍然开放以进行应计。这些疾病实体都是 癌症存在毁灭性的、无法治愈的神经系统并发症 治疗是不够的。单抗的发展已经 为更特异地治疗肿瘤提供了可能性，这些肿瘤 与所述单抗或抗体片段发生反应。抗体 它们是肿瘤细胞所特有的，不与正常细胞发生反应 大脑或脊髓可以与治疗性放射性同位素结合， 如131I。然后这种结合物可以在鞘内给药 软脑膜肿瘤，植入自然形成的肿瘤囊腔内治疗 囊性脑瘤，或进入外科手术创建的切除腔 实体脑瘤将提供治疗量的放射治疗 对肿瘤细胞的相对特异性。放射性标记的单抗 抗体可能是治疗这些疾病的一种重要的新疗法。 实体。这是美国第一次对这种情况进行测试 软脑膜肿瘤和脑肿瘤的分区治疗 用放射性标记的单抗切除空洞。