2012
A Multicenter Phase I Trial of PX-866, an Oral Irreversible Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Advanced Solid Tumors
Hong DS, Bowles DW, Falchook GS, Messersmith WA, George GC, O'Bryant CL, Vo AC, Klucher K, Herbst RS, Eckhardt SG, Peterson S, Hausman DF, Kurzrock R, Jimeno A. A Multicenter Phase I Trial of PX-866, an Oral Irreversible Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Advanced Solid Tumors. Clinical Cancer Research 2012, 18: 4173-4182. PMID: 22693357, DOI: 10.1158/1078-0432.ccr-12-0714.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAged, 80 and overArea Under CurveDiarrheaDisease ProgressionDose-Response Relationship, DrugDrug Administration ScheduleEnzyme InhibitorsFatigueFemaleGonanesHumansMaleMetabolic Clearance RateMiddle AgedMutationNauseaNeoplasmsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsTreatment OutcomeVomitingConceptsDose-limiting toxicityArm 1PX-866Stable diseaseArm 2Frequent study drug-related adverse eventsSolid tumorsStudy drug-related adverse eventsDrug-related adverse eventsMulticenter phase I trialGrade III diarrheaAdvanced solid tumorsDose-escalation studyResponse Evaluation CriteriaContinuous dosing scheduleElevated aspartate aminotransferasePhase I trialEvaluable patientsIrreversible small-molecule inhibitorAdverse eventsDosing schedulesI trialAdditional patientsGastrointestinal disordersIncurable cancer
2009
Phase I trial of PX-866, a novel phosphoinositide-3-kinase (PI-3K) inhibitor
Jimeno A, Hong D, Hecker S, Clement R, Kurzrock R, Pestano L, Hiscox A, Leos R, Kirkpatrick D, Eckhardt S, Herbst R. Phase I trial of PX-866, a novel phosphoinositide-3-kinase (PI-3K) inhibitor. Journal Of Clinical Oncology 2009, 27: 3542-3542. DOI: 10.1200/jco.2009.27.15_suppl.3542.Peer-Reviewed Original ResearchPX-866Stable diseaseClinical trialsDay 1Drug-related severe adverse eventsMild side effect profilePhase 1 clinical trialStabilization of diseaseSevere adverse eventsDose-limiting toxicityPhase I trialSide effect profileAdvanced metastatic cancerP-mTOR levelsDose-dependent inhibitionLower drug dosesPhosphoinositide-3 kinase inhibitorPD endpointsExpansion cohortLast doseAbdominal discomfortAdverse eventsI trialEffect profileLoss of PTEN