Orally administered colony stimulating factor 1 receptor inhibitor PLX3397 in recurrent glioblastoma: an Ivy Foundation Early Phase Clinical Trials Consortium phase II study
Butowski N, Colman H, De Groot JF, Omuro AM, Nayak L, Wen PY, Cloughesy TF, Marimuthu A, Haidar S, Perry A, Huse J, Phillips J, West BL, Nolop KB, Hsu HH, Ligon KL, Molinaro AM, Prados M. Orally administered colony stimulating factor 1 receptor inhibitor PLX3397 in recurrent glioblastoma: an Ivy Foundation Early Phase Clinical Trials Consortium phase II study. Neuro-Oncology 2015, 18: 557-564. PMID: 26449250, PMCID: PMC4799682, DOI: 10.1093/neuonc/nov245.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAminopyridinesBiomarkers, TumorBlood-Brain BarrierBrain NeoplasmsCohort StudiesFemaleFollow-Up StudiesGlioblastomaHumansImmunoenzyme TechniquesMaleMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingPrognosisPyrrolesReceptors, Granulocyte-Macrophage Colony-Stimulating FactorTissue DistributionTumor BurdenConceptsPhase II studyII studyRecurrent glioblastomaTumor tissueMedian drug levelsPrimary efficacy endpointProgression-free survivalBlood-brain barrierPretreatment baseline valuesBlood-tumor barrierExploratory endpointsInhibitor PLX3397Efficacy endpointPrimary endpointSecondary endpointsObjective responseSurgical resectionOral dosePharmacodynamic changesPharmacodynamic measuresTumor burdenDrug exposureTissue pharmacokineticsDrug levelsStem cell factorPhase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma
Wen PY, Omuro A, Ahluwalia MS, Fathallah-Shaykh HM, Mohile N, Lager JJ, Laird AD, Tang J, Jiang J, Egile C, Cloughesy TF. Phase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma. Neuro-Oncology 2015, 17: 1275-1283. PMID: 26019185, PMCID: PMC4588757, DOI: 10.1093/neuonc/nov083.Peer-Reviewed Original ResearchConceptsHigh-grade gliomasAdverse eventsRadiation therapySkin biopsiesPhase I dose-escalation studyTreatment-related adverse eventsI dose-escalation studyPI3K/mTOR pathway inhibitionTreatment-related gradeDose-escalation studyDose-escalation designFavorable safety profileMTOR pathway inhibitionEvaluable patientsStable diseasePartial responsePharmacodynamic effectsPlatelet countRapamycin inhibitorsSafety profilePreliminary efficacyTumor responsePlasma pharmacokineticsVoxtalisibPatients