2020
Phase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma
Kaley TJ, Panageas KS, Pentsova EI, Mellinghoff IK, Nolan C, Gavrilovic I, DeAngelis LM, Abrey LE, Holland EC, Omuro A, Lacouture ME, Ludwig E, Lassman AB. Phase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma. Annals Of Clinical And Translational Neurology 2020, 7: 429-436. PMID: 32293798, PMCID: PMC7187704, DOI: 10.1002/acn3.51009.Peer-Reviewed Original ResearchConceptsRecurrent malignant gliomaDose-limiting toxicityMTOR inhibitor temsirolimusMalignant gliomasAkt inhibitor perifosinePhase I clinical trialDose level 3Dose level 7Phase II doseSynergistic anti-tumor effectKarnofsky performance statusPhase I trialDeadly primary brain cancerPI3K/Akt/mTOR axisPrimary brain cancerAkt/mTOR axisAnti-tumor effectsPotential therapeutic targetMost malignant gliomasPrior therapyTemsirolimus dosePerformance statusI trialIntracerebral hemorrhageCombined therapy
2015
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
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
2007
Lessons learned in the development of targeted therapy for malignant gliomas
Omuro AM, Faivre S, Raymond E. Lessons learned in the development of targeted therapy for malignant gliomas. Molecular Cancer Therapeutics 2007, 6: 1909-1919. PMID: 17620423, DOI: 10.1158/1535-7163.mct-07-0047.Peer-Reviewed Original ResearchMeSH KeywordsClinical Trials as TopicGliomaHumansProtein Kinase CProtein Kinase C betaProtein KinasesReceptors, Cell SurfaceTOR Serine-Threonine KinasesConceptsVascular endothelial growth factor receptorEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsReceptor tyrosine kinase inhibitorsPreliminary efficacy resultsPrognosis of patientsTranslational researchEndothelial growth factor receptorEffective treatment optionTyrosine kinase inhibitorsGrowth factor receptorRecurrent diseaseRapamycin inhibitorsPreclinical dataStandard treatmentTreatment optionsEfficacy resultsMalignant gliomasSuch tumorsNovel agentsAnaplastic astrocytomaMost trialsTrial designProtein kinase C betaPathway inhibitor