This is an investigator initiated, NCI approved protocol designed to determine the maximum tolerated dose of 90Y-CC49 monoclonal antibody with alpha-interferon (IFN) in patients with advanced non-small cell lung cancer. All patients will have tissue diagnosis of metastatic or unresectable non- small cell lung carcinoma. Tumor specimens will be tested for TAG-72 using immunoperoxidase staining of tumor block (Dr. William E. Grizzle's laboratory). Patients with at least 10% positivity for immunoreactivity with TAG-72 will be considered for this study. The patients will be entered onto the study in sets of at least three patients per dose level until the maximal tolerated dose (MTD) is identified. The pre-study evaluation will be done in the clinic, and patients will be instructed to self-administer interferon therapy at home. Thereafter, patients will be admitted for three days at the General Clinical Research Center for antibody therapy. Patients will be monitored for adverse reactions, antitumor effects, pharmacokinetics, imaging, dosimetry, and immune response. The initial dose of intravenous 90Y-C49-PA-DOTA will be 8 mCi/m2 in an antibody dose of 10 mg of CC49, infused over 30 minutes on day 1. This therapy will be preceded by 100 5g test dose of cold (unlabeled) CC49 and a 10 minute infusion of 111IN-CC49-PD-DOTA (5 mCi). Subsequent dose escalation will be on the basis of 2.0 mCi/m2 per dose level with different groups of patients until the MTD is reached. Toxicity data from each dose level will be submitted to NCI for review prior to proceeding to the next dose level. When the MTD dose is reached, then a different group of 5 patients will be treated at the same dose level of 90Y-CC49- with calcium disodium EDTA. Six 12-hour continuous intravenous infusions of 25 mg calcium sodium EDTA per Kg of patient body weight in 500 ml 0.9% saline will be administered starting 30 minutes prior to the 90Y-CC49 infusion. If EDTA co- administration results in bone marrow suppression less than MTD guidelines, dose escalation at increments of 2.0 mCi/m2 90Y-CC49 will continue with EDTA until new MTD is established.
NIH ExPorter
NIH ExPorter