Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase, in patients with advanced solid tumors.
The purpose of this study was to determine the maximum-tolerated dose (MTD), pharmacokinetics and safety profile for two different dosing regimens of barasertib, a selective inhibitor of Aurora B Kinase. In this Phase I trial, patients with advanced solid malignancies were treated with escalating do...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2013
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| _version_ | 1797067186201690112 |
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| author | Schwartz, G Carvajal, R Midgley, R Rodig, S Stockman, P Ataman, O Wilson, D Das, S Shapiro, G |
| author_facet | Schwartz, G Carvajal, R Midgley, R Rodig, S Stockman, P Ataman, O Wilson, D Das, S Shapiro, G |
| author_sort | Schwartz, G |
| collection | OXFORD |
| description | The purpose of this study was to determine the maximum-tolerated dose (MTD), pharmacokinetics and safety profile for two different dosing regimens of barasertib, a selective inhibitor of Aurora B Kinase. In this Phase I trial, patients with advanced solid malignancies were treated with escalating doses of barasertib, administered as either a 48-h continuous infusion or as two 2-h infusions on consecutive days, both every 14 days of a 28-day cycle. Thirty-five patients were treated. The MTDs were 150 mg as a 48-h continuous infusion and 220 mg administered as two 2-h infusions (110 mg/day, days 1, 2, 15 and 16), with neutropenia the dose-limiting toxicity (DLT) of each schedule. Common Terminology Criteria of Adverse Events (CTCAE) grade ≥ 3 neutropenia (with or without fever) occurred in 34% of patients overall. Other adverse events, many of hematologic or gastrointestinal etiology, were of mild or moderate intensity. No objective tumor responses were observed, although stable disease was observed in 23% of patients. Systemic exposure to barasertib-hQPA, the more active moiety to which barasertib is converted, was observed by 1 and 6 h into the 2-h and continuous infusion, respectively, and exhibited linear pharmacokinetics. In summary, barasertib was generally well tolerated, with neutropenia the most frequent and dose-limiting toxicity, irrespective of schedule. Future development of barasertib will depend on better definition of its therapeutic index. |
| first_indexed | 2024-03-06T21:52:45Z |
| format | Journal article |
| id | oxford-uuid:4bdd8218-f1a3-497a-a333-d7f60cdf3106 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:52:45Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:4bdd8218-f1a3-497a-a333-d7f60cdf31062022-03-26T15:46:12ZPhase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase, in patients with advanced solid tumors.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4bdd8218-f1a3-497a-a333-d7f60cdf3106EnglishSymplectic Elements at Oxford2013Schwartz, GCarvajal, RMidgley, RRodig, SStockman, PAtaman, OWilson, DDas, SShapiro, GThe purpose of this study was to determine the maximum-tolerated dose (MTD), pharmacokinetics and safety profile for two different dosing regimens of barasertib, a selective inhibitor of Aurora B Kinase. In this Phase I trial, patients with advanced solid malignancies were treated with escalating doses of barasertib, administered as either a 48-h continuous infusion or as two 2-h infusions on consecutive days, both every 14 days of a 28-day cycle. Thirty-five patients were treated. The MTDs were 150 mg as a 48-h continuous infusion and 220 mg administered as two 2-h infusions (110 mg/day, days 1, 2, 15 and 16), with neutropenia the dose-limiting toxicity (DLT) of each schedule. Common Terminology Criteria of Adverse Events (CTCAE) grade ≥ 3 neutropenia (with or without fever) occurred in 34% of patients overall. Other adverse events, many of hematologic or gastrointestinal etiology, were of mild or moderate intensity. No objective tumor responses were observed, although stable disease was observed in 23% of patients. Systemic exposure to barasertib-hQPA, the more active moiety to which barasertib is converted, was observed by 1 and 6 h into the 2-h and continuous infusion, respectively, and exhibited linear pharmacokinetics. In summary, barasertib was generally well tolerated, with neutropenia the most frequent and dose-limiting toxicity, irrespective of schedule. Future development of barasertib will depend on better definition of its therapeutic index. |
| spellingShingle | Schwartz, G Carvajal, R Midgley, R Rodig, S Stockman, P Ataman, O Wilson, D Das, S Shapiro, G Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase, in patients with advanced solid tumors. |
| title | Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase, in patients with advanced solid tumors. |
| title_full | Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase, in patients with advanced solid tumors. |
| title_fullStr | Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase, in patients with advanced solid tumors. |
| title_full_unstemmed | Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase, in patients with advanced solid tumors. |
| title_short | Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase, in patients with advanced solid tumors. |
| title_sort | phase i study of barasertib azd1152 a selective inhibitor of aurora b kinase in patients with advanced solid tumors |
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