monoclonal antibody therapy in treating patients with primary or metastatic melanoma or brain tumors

Conditions: Brain and Central Nervous System Tumors; Melanoma (Skin); Metastatic Cancer

Summary: rationale: monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. purpose: phase i/ii trial to determine the effectiveness of monoclonal antibody therapy in treating patients who have primary or metastatic melanoma or brain tumors.

objectives: i. determine the toxicity and maximum tolerated dose of iodine-131-labeled monoclonal antibody fragment me1-14 f(ab')2 administered intracystically in patients with recurrent or newly diagnosed primary or metastatic malignant melanoma or other brain tumors. ii. identify any objective therapeutic responses to this treatment. outline: all patients receive a fixed dose of monoclonal antibody fragment me1-14 f(ab')2 via an intralesional catheter; cohorts of 3-6 patients receive escalating doses of isotope conjugated to the antibody until the maximum tolerated dose is determined. patients with newly diagnosed disease at entry may receive additional therapy with external-beam radiotherapy beginning 4 months after radioimmunotherapy (or sooner if disease progression occurs). patients with recurrent disease at entry are followed without further therapy for at least 4 months after radioimmunotherapy; alternative therapy may be offered upon progression. all patients are followed at 4, 8, 16, and 24 weeks after treatment, then every 12 weeks for 1 year. projected accrual: three to six patients will be entered at each dose studied.

Eligibility criteria:
disease characteristics: histologically confirmed primary or metastatic malignant melanoma or histologically confirmed supratentorial malignant brain tumor newly diagnosed or recurrent primary or metastatic tumor eligible primary histologies, including but not limited to: glioblastoma multiforme mixed anaplastic glioma anaplastic astrocytoma other astrocytoma gliosarcoma anaplastic oligodendroglioma the following excluded: diffusely infiltrating tumors multifocal tumors infratentorial tumors subependymal spread no measurable enhancing lesion extending more than 1 cm beyond margins of surgical cavity on contrast-enhanced ct or mri performed within 72 hours after resection intralesional catheter placed at resection patency of catheter demonstrated by radiolabeled albumin flow reactivity of neoplastic cells with intact me1-14 igg2a or me1-14 f(ab')2 demonstrated by immunohistology with polyclonal rabbit antibody or monoclonal mouse antibody patient characteristics: age: 3 and over performance status: karnofsky 50%-100% hematopoietic: absolute neutrophil count greater than 1,000/mm3 platelet count greater than 100,000/mm3 hepatic: bilirubin less than 1.5 mg/dl ast less than 1.5 times normal alkaline phosphatase less than 1.5 times normal renal: creatinine less than 1.2 mg/dl other: not pregnant prior concurrent therapy: biologic therapy: not specified chemotherapy: at least 6 weeks since antineoplastic chemotherapy unless unequivocal tumor progression endocrine therapy: concurrent corticosteroids allowed at lowest possible dose and stable for at least 10 days prior to entry radiotherapy: at least 3 months since radiotherapy to site of measurable disease within the nervous system unless unequivocal tumor progression surgery: see disease characteristics

Keywords: recurrent adult brain tumor adult glioblastoma stage iv melanoma tumors metastatic to brain childhood high-grade cerebral astrocytoma adult anaplastic astrocytoma adult anaplastic oligodendroglioma adult mixed glioma recurrent childhood cerebral astrocytoma adult giant cell glioblastoma adult gliosarcoma