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.
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