A Phase Ib, open-label, dose-finding study of alpelisib in combination with paclitaxel in patients with advanced solid tumors

Oncotarget
Jordi RodonThaddeus Beck

Abstract

Phosphatidylinositol 3-kinase (PI3K) pathway activation is associated with resistance to paclitaxel in solid tumors. We assessed the safety and activity of alpelisib, an oral, selective PI3K p110α inhibitor, plus paclitaxel in patients with advanced solid tumors. This Phase Ib, multicenter, open-label, dose-finding study, with a planned dose-expansion phase of alpelisib once daily (QD) plus fixed-dose paclitaxel, recruited patients with advanced solid tumors. For the dose-finding phase, the primary objective was determination of maximum tolerated and/or recommended Phase II dose of alpelisib plus paclitaxel, and the secondary objectives included the assessment of safety for this combination. From March 2014 to August 2016, 19 patients with advanced solid tumors were treated with alpelisib QD (300 mg, n=6; 250 mg, n=4; 150 mg, n=9) plus paclitaxel (80 mg/m2, per standard of care). During dose finding, five of 12 (41.7%) evaluable patients for MTD determination experienced dose-limiting toxicities: alpelisib 300 mg, Grade 2 hyperglycemia (n=1); alpelisib 250 mg, Grade 2 hyperglycemia (n=1), Grade 4 hyperglycemia and Grade 3 acute kidney injury (n=1); and alpelisib 150 mg, Grade 2 hyperglycemia (n=1) and Grade 4 leukopenia (n=1). ...Continue Reading

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Citations

Jan 17, 2019·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Giuseppe Curigliano, Rashmi R Shah
Sep 24, 2020·Future Oncology·Athanasios Mavratzas, Frederik Marmé
Jul 1, 2020·Clinics and Research in Hepatology and Gastroenterology·Coralie Cayron, Julie Guillermet-Guibert
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Mar 20, 2021·The Biochemical Journal·Silvia ArcucciJulie Guillermet-Guibert
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Clinical Trials Mentioned

NCT01219699
NCT02437318
NCT03056755

Software Mentioned

BYLieve

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