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
2017
Phase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas
Nayak L, de Groot J, Wefel JS, Cloughesy TF, Lieberman F, Chang SM, Omuro A, Drappatz J, Batchelor TT, DeAngelis LM, Gilbert MR, Aldape KD, Yung AW, Fisher J, Ye X, Chen A, Grossman S, Prados M, Wen PY. Phase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas. Journal Of Neuro-Oncology 2017, 132: 181-188. PMID: 28116649, PMCID: PMC5588922, DOI: 10.1007/s11060-016-2357-9.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, AlkylatingBrain NeoplasmsChemotherapy, AdjuvantCombined Modality TherapyDacarbazineDrug Therapy, CombinationFemaleGliomaHumansMaleMiddle AgedNeuropsychological TestsReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsTemozolomideTreatment OutcomeVascular Endothelial Growth Factor AConceptsHigh-grade gliomasPhase I trialI trialArm 2Arm 1Anti-vascular endothelial growth factor therapyAdult Brain Tumor ConsortiumEndothelial growth factor therapyRecombinant human fusion proteinGrowth factorFull treatment courseGrowth factor therapyPlacental growth factorSoluble decoy receptorHuman fusion proteinKPS 90Primary endpointFactor therapyDay regimenMedian ageTreatment courseArm 3Disease progressionMedian numberRadiation 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