title: A phase I multiple dose, dose escalation study of cG250 monoclonal antibody in patients with advanced renal cell carcinoma.
abstract: The chimeric monoclonal antibody cG250 recognises the G250/CAIX/MN antigen found on 95% of clear cell renal cell carcinomas (RCCs). We performed a phase I clinical trial to evaluate the safety, blood pharmacokinetics (PK), and biodistribution of repeated doses of cG250. The primary endpoint was toxicity. Secondary endpoints were cG250 biodistribution and PK; measurement of human anti-chimeric-antibodies (HACA); and tumour response rates. Eligible patients had unresectable or metastatic clear cell RCC. Doses of 5, 10, 25, or 50 mg/m(2) were given weekly by intravenous infusion for six weeks. Three patients were treated at each dose level. Trace (131)I-labelled cG250 was administered on weeks 1 and 5. Thirteen patients participated and were evaluable. One patient developed brain metastases and was replaced. No grade 3 or 4 toxicities and no dose-limiting toxicity occurred. One patient died due to progressive disease within 30 days of receiving the study drug. One patient developed HACA during the second six-week cycle. PK analysis showed mean whole body and blood alpha and beta half-lives of cG250 of 18.99 +/- 6.84 and 180.19 +/- 86.68 hours, respectively. All patients had cG250 tumour localization by gamma camera imaging in week 1 and 5. One patient had a complete response, nine patients had stable disease, and three had progressive disease. One patient received 11 six-week cycles of treatment with no toxicity or HACA. In conclusion, repeated intravenous doses of up to 50 mg/m(2) of cG250 are safe. Furthermore cG250 has a long half-life and targets clear cell RCC effectively.
authors: Ludwig Institute for Cancer Research, Victoria, Australia. Ian.Davis@ludwig.edu.au
authors: Ian D
authors: ID
authors: Davis
authors: Gregory A
authors: GA
authors: Wiseman
authors: Fook-Thean
authors: FT
authors: Lee
authors: Denise N
authors: DN
authors: Gansen
authors: Wendie
authors: W
authors: Hopkins
authors: Anthony T
authors: AT
authors: Papenfuss
authors: Zhanqi
authors: Z
authors: Liu
authors: Timothy J
authors: TJ
authors: Moynihan
authors: Gary A
authors: GA
authors: Croghan
authors: Alex A
authors: AA
authors: Adjei
authors: Eric W
authors: EW
authors: Hoffman
authors: James N
authors: JN
authors: Ingle
authors: Lloyd J
authors: LJ
authors: Old
authors: Andrew M
authors: AM
authors: Scott
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000276:immunology / Q000628:therapy*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C106533:G250 monoclonal antibody; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
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