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A phase 2, randomized study of SB‐485232, rhIL‐18, in patients with previously untreated metastatic melanoma
Author(s) -
Tarhini Ahmad A.,
Millward Michael,
Mainwaring Paul,
Kefford Richard,
Logan Ted,
Pavlick Anna,
Kathman Steven J.,
Laubscher Kevin H.,
Dar Mohammed M.,
Kirkwood John M.
Publication year - 2009
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.24100
Subject(s) - medicine , adverse effect , discontinuation , gastroenterology , pulmonary embolism , deep vein , randomized controlled trial , melanoma , thrombosis , surgery , cancer research
BACKGROUND: Phase 1 studies demonstrated evidence of recombinant human IL‐18 (rhIL‐18)‐mediated immunomodulatory and clinical activity, and defined a biologically active dose range. METHODS: A phase 2 study of rhIL‐18 was conducted in untreated AJCC stage IV melanoma. Patients were randomized to 1 of 3 dose groups (0.01, 0.1, and 1.0 mg/kg/d) of rhIL‐18 administered as 5 daily intravenous infusions repeated every 28 days. A 2‐stage design with a stopping rule was used. RESULTS: A total of 64 patients (median age, 57.5 years) with metastatic melanoma (M1a/b (30), M1c (34)) were accrued to stage I, and randomized to 3 groups (21 [0.01 mg/kg/d], 21 [0.1 mg/kg/d], 22 [1.0 mg/kg/d]). Five patients experienced 10 grade 3 drug‐related adverse events (AEs): polyarthritis (1 subject: 0.01 mg/kg); deep vein thrombosis, pulmonary embolism (1:0.01 mg/kg); cognitive disorder (1:0.1 mg/kg); fatigue, dyspnea, pleural effusion, lymphopenia (1:1.0 mg/kg); fatigue, lymphopenia (1:1.0 mg/kg). One patient experienced a grade 4 AE of increased lipase (0.1 mg/kg) that led to permanent discontinuation from the study. Among 63 subjects evaluable for response, 1 (M1c; 0.01 mg/kg) achieved a partial response after 4 cycles. Four subjects (3 at 0.01 mg/kg and 1 at 1.0 mg/kg) had stable disease maintained for 6 months or longer. Due to the low apparent level of clinical efficacy using RECIST criteria, the study was terminated at the end of stage 1. The median progression free survival for the 3 groups was 7.5 (0.01), 7.4 (0.1), and 7.3 (1.0) weeks. CONCLUSIONS: rIL‐18 as tested in this trial was well tolerated, but had limited activity as a single agent in patients with metastatic melanoma. Cancer 2009. © 2009 American Cancer Society.