MONOCLONAL ANTIBODY 81C6-131I METASTATIC TO LEPTOMENINGES

本方案包含两个组成部分，每个组成部分均分配有单独的杜克IRB number.第一种成分使用131 I标记的81 C6单克隆抗体 抗体治疗肿瘤性脑膜炎患者，或 术后囊性脑肿瘤切除腔与 脑脊液。 本研究的目的是确定 鞘内注射131 I标记的81 C6单克隆抗体治疗 肿瘤性脑膜炎或术后囊性脑肿瘤 切除腔与脑脊液相通。 第二部件 利用131 I标记的81 C6单克隆抗体治疗 恶性中枢神经系统肿瘤患者， 创建囊性切除腔（不与CSF连通）。 本研究的目的是确定131 I标记的 将81 C6单克隆抗体施用到手术创建的囊性 肿瘤切除术后空洞 恶性中心性 神经系统肿瘤 这两种疾病都是毁灭性的，无法治愈的 癌症的神经系统并发症，目前的治疗方法 不足 单克隆抗体的发展提供了 潜在的更具体的治疗肿瘤，是反应性与 单克隆抗体或抗体片段。 的抗体 特异于肿瘤细胞，不与正常大脑反应， 脊髓可以与治疗性放射性同位素结合，例如 131 I. 然后可以将该缀合物鞘内递送， 软脑膜肿瘤或植入手术创建的切除腔 对脑肿瘤进行治疗剂量的放射治疗 肿瘤细胞的相对特异性。 ~（131）I标记的~（81）C_6单克隆抗体用于临床的Ⅱ期研究 肿瘤性脑膜炎或术后囊性空洞 与CSF通信（CRU协议753），建立在成功的 完成针对患者的I期研究CRU方案648 转移到软脑膜的肿瘤。 在II期研究中， 符合条件的患者每月接受60 mCi鞘内注射治疗 131 I标记的81 C6单克隆抗体（10 mg蛋白质）。患者 每八周评估一次反应。 响应标准基于 脑脊液细胞学和MRI扫描肿瘤大小的客观测量。 为 对于复发性肿瘤患者，治疗将持续到 完全缓解12个周期，疾病稳定12个周期， 通过MRI或体格检查记录的进行性或复发性疾病， 4级非血液学毒性或需要 再输注患者先前储存的外周干细胞。 新诊断的肿瘤患者，没有有效的常规治疗方法 治疗存在，如恶性胶质细胞 肿瘤转移到 软脑膜，治疗4个周期，然后转到外部 放射线治疗，除非在较早的时间注意到进行性肿瘤。 新诊断患者治疗持续时间的其他标准 与复发性肿瘤患者相同。中的每 5个组织学亚组，两阶段II期设计， 10%至30%的回复率将用于评估 鞘内131 I标记的81 C6的活性。

This protocol contains two components, each assigned a separate Duke IRB number. The first component utilizes 131I-labeled 81C6 monoclonal antibody in the treatment of patients with neoplastic meningitis or postoperative cystic brain tumor resection cavities communicating with CSF. The purpose of this study is to determine the efficacy of intrathecal 131I-labeled 81C6 monoclonal antibody in patients with neoplastic meningitis or postoperative cystic cystic brain tumor resection cavities communicating with CSF. The second component utilizes 131I-labeled 81C6 monoclonal antibody in the treatment of patients with malignant central nervous system tumors with surgically created cystic resection cavities (that do not communicate with CSF). The purpose of this study is to determine the efficacy of 131I-labeled 81C6 monoclonal antibody administered into surgically created cystic tumor resection cavities in patients with malignant central nervous system tumors. Both disease entities are 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 or into a surgically-created resection cavity for brain tumors to deliver a therapeutic dose of radiation with relative specificity for the tumor cells. The Phase II study of 131I-labeled 81C6 monoclonal antibody for patients with neoplastic meningitis or postoperative cystic cavities communicating with CSF (CRU Protocol 753), builds on the successful completion of the Phase I study CRU Protocol 648 for patients with neoplasms metastatic to the leptomeninges. In the Phase II study, eligible patients are treated with monthly cycles of intrathecal 60 mCi 131I-labeled 81C6 monoclonal antibody (10 mg protein). Patients are evaluated for response each eight weeks. Response criteria are based on objective measures of CSF cytology and tumor size on MRI scanning. For patients with recurrent tumors, treatment continues until there has been a complete response for 12 cycles, stable disease for 12 cycles, progressive or recurrent disease as documented by MRI or physical exam, grade 4 nonhematologic toxicity or hematologic toxicity requiring reinfusion of the patient's previously stored peripheral stem cells. Patients with newly diagnosed tumors for which no effective conventional therapy exists, such as malignant glial tumors metastatic to the leptomeninges, are treated for 4 cycles and then referred to external beam radiotherapy unless progressive tumor is noted at an earlier time. The other criteria for treatment duration in newly diagnosed patients are the same as those for patients with recurrent tumors. For each of 5 histologic subgroups, a two-stage Phase II design which differentiates between a response rate of 10% and 30% will be used to evaluate the activity of intrathecal 131I-labeled 81C6.