دورية أكاديمية
أعرض في EDS

Phase II study of alisertib as a single agent for treating recurrent or progressive atypical teratoid/rhabdoid tumor.

التفاصيل البيبلوغرافية
العنوان: Phase II study of alisertib as a single agent for treating recurrent or progressive atypical teratoid/rhabdoid tumor.
المؤلفون: Upadhyaya SA; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Campagne O; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Billups CA; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Orr BA; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Onar-Thomas A; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Tatevossian RG; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Mostafavi R; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Myers JR; Center for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Vinitsky A; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Moreira DC; Department of Global Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Lindsay HB; Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA., Kilburn L; Division of Oncology, Children's National Medical Center, Washington, DC, USA., Baxter P; Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA., Smith A; Department of Hematology and Oncology, Arnold Palmer Hospital for Children, Orlando, Florida, USA., Crawford JR; Department of Neurosciences and Pediatrics, University of California, San Diego and Rady Children's Hospital, San Diego, California, USA., Partap S; Department of Neurology, Stanford University, Palo Alto, California, USA., Bendel AE; Department of Hematology Oncology, Children's Minnesota, Minneapolis, Minnesota, USA., Aguilera DG; Aflac Cancer and Blood Disorders Center, Atlanta, Georgia, USA., Nichols KE; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Rampersaud E; Center for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Ellison DW; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Klimo P; Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Patay Z; Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Robinson GW; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Broniscer A; Division of Hematology Oncology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA., Stewart CF; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Wetmore C; Clinical Development, Neolukin Therapeutics, Seattle, USA., Gajjar A; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.; Department of Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
المصدر: Neuro-oncology [Neuro Oncol] 2023 Feb 14; Vol. 25 (2), pp. 386-397.
نوع المنشور: Clinical Trial, Phase II; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 100887420 Publication Model: Print Cited Medium: Internet ISSN: 1523-5866 (Electronic) Linking ISSN: 15228517 NLM ISO Abbreviation: Neuro Oncol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2010- : Oxford : Oxford University Press
Original Publication: 1999-<2002> : Charlottesville, VA : Carden Jennings Pub.,
مواضيع طبية MeSH: Antineoplastic Agents*/therapeutic use , Rhabdoid Tumor*/drug therapy , Central Nervous System Neoplasms*/drug therapy, Child ; Humans ; Azepines/therapeutic use ; Pyrimidines/therapeutic use ; Aurora Kinase A ; Protein Kinase Inhibitors/therapeutic use ; Protein Kinase Inhibitors/adverse effects
مستخلص: Background: Recurrent atypical teratoid/rhabdoid tumor (AT/RT) is, most often, a fatal pediatric malignancy with limited curative options.
Methods: We conducted a phase II study of Aurora kinase A inhibitor alisertib in patients aged <22 years with recurrent AT/RT. Patients received alisertib once daily (80 mg/m2 as enteric-coated tablets or 60 mg/m2 as liquid formulation) on Days 1-7 of a 21-day cycle until progressive disease (PD) occurred. Alisertib plasma concentrations were measured in cycle 1 on Days 1 (single dose) and 7 (steady state) and analyzed with noncompartmental pharmacokinetics. Trial efficacy end point was ≥10 participants with stable disease (SD) or better at 12 weeks.
Results: SD (n = 8) and partial response (PR) (n = 1) were observed among 30 evaluable patients. Progression-free survival (PFS) was 30.0% ± 7.9% at 6 months and 13.3% ± 5.6% at 1 year. One-year overall survival (OS) was 36.7% ± 8.4%. Two patients continued treatment for >12 months. PFS did not differ by AT/RT molecular groups. Neutropenia was the most common adverse effect (n = 23/30, 77%). The 22 patients who received liquid formulation had a higher mean maximum concentration (Cmax) of 10.1 ± 3.0 µM and faster time to Cmax (Tmax = 1.2 ± 0.7 h) than those who received tablets (Cmax = 5.7 ± 2.4 µM, Tmax = 3.4 ± 1.4 h).
Conclusions: Although the study did not meet predetermined efficacy end point, single-agent alisertib was well tolerated by children with recurrent AT/RT, and SD or PR was observed in approximately a third of the patients.
(© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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معلومات مُعتمدة: P30 CA021765 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Aurora kinase A; alisertib; alisertib pharmacokinetics; atypical teratoid/rhabdoid tumor
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (MLN 8237)
0 (Azepines)
0 (Pyrimidines)
EC 2.7.11.1 (Aurora Kinase A)
0 (Protein Kinase Inhibitors)
تواريخ الأحداث: Date Created: 20220602 Date Completed: 20230215 Latest Revision: 20230603
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9925713
DOI: 10.1093/neuonc/noac151
PMID: 35652336
قاعدة البيانات: MEDLINE
الوصف
تدمد:1523-5866
DOI:10.1093/neuonc/noac151