Multicentric parallel phase II trial of the polo-like kinase 1 inhibitor BI 2536 in patients with advanced head and neck cancer, breast cancer, ovarian cancer, soft tissue sarcoma and melanoma : the first protocol of the European Organization for Research and Treatment of Cancer (EORTC) Network Of Core Institutes (NOCI)

Schöffski, Patrick;Blay, Jean-Yves;De Greve, Jacques;Brain, Etienne;Lacombe, Denis;et.al.
(2010) European Journal of Cancer — Vol. 46, n° 12, p. 2206-2215 (2010)

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Authors
  • Schöffski, PatrickKUL
    Author
  • Blay, Jean-Yves
    Author
  • De Greve, Jacques
    Author
  • Brain, Etienne
    Author
  • Machiels, Jean-PascalUCLouvain
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  • Lacombe, Denis
    Author
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Abstract
Aims: BI 2536 is a selective and potent small-molecule inhibitor of polo-like kinase 1. We performed a multi-centre, multi-tumour phase II trial to investigate the efficacy, safety and pharmacokinetics of BI 2536 in five solid tumour types. Patients and methods: Patients with advanced head and neck, breast and ovarian cancer, soft tissue sarcoma and melanoma were selected according to protocol-defined general and tumour-specific criteria. They were >= 18 years old, had a good performance status, adequate bone marrow, renal and liver function, measurable progressive disease and had completed other relevant systemic treatments >4 weeks ago. BI 2536 200-250 mg was given intravenously on day 1 every 3 weeks until intolerance, progression or refusal. The study was based on a Simon two-stage design, with 12 patients entering in stage 1 and additional 25 patients to be entered in case of at least one response in the first stage. The rate of objective responses (RECIST criteria) was chosen as primary end-point. Results: Seventy six patients were included, 71 started treatment and received a median number of two cycles (four in ovarian cancer). Frequent grade 3-4 adverse events were neutropaenia (81.6%), thrombocytopaenia (19.7%), febrile neutropaenia (19.7%), anaemia (15.5%) and pain (9.9%). We did not observe confirmed objective responses. All cohorts were closed after the entry of 14-15 eligible non-responding patients. Pharmacokinetic analyses revealed multi-compartmental behaviour and a rapid distribution of BI 2536. Conclusions: BI 2536 showed limited antitumour activity according to the design of this trial in five different tumour types. Derivatives of BI 2536 with a more favourable pharmacological profile are currently explored further in prospective studies. (C) 2010 Elsevier Ltd. All rights reserved.
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Schöffski, P., Blay, J.-Y., De Greve, J., Brain, E., Machiels, J.-P., Soria, J.-C., Sleijfer, S., Wolter, P., Ray-Coquard, I., Fontaine, C., Munzert, G., Fritsch, H., Hanft, G., Aerts, C., Rapion, J., Allgeier, A., Bogaerts, J., & Lacombe, D. (2010). Multicentric parallel phase II trial of the polo-like kinase 1 inhibitor BI 2536 in patients with advanced head and neck cancer, breast cancer, ovarian cancer, soft tissue sarcoma and melanoma : the first protocol of the European Organization for Research and Treatment of Cancer (EORTC) Network Of Core Institutes (NOCI). European Journal of Cancer, 46(12), 2206-2215. https://doi.org/10.1016/j.ejca.2010.03.039 (Original work published 2010)