MONOCLONAL ANTIBODY 81C6-131I METASTATIC TO LEPTOMENINGES

该协议包含两个组件，每个组件分配一个单独的杜克大学IRB

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.