2019
Buparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial
Wen PY, Touat M, Alexander BM, Mellinghoff IK, Ramkissoon S, McCluskey CS, Pelton K, Haidar S, Basu SS, Gaffey SC, Brown LE, Martinez-Ledesma JE, Wu S, Kim J, Wei W, Park MA, Huse JT, Kuhn JG, Rinne ML, Colman H, Agar NYR, Omuro AM, DeAngelis LM, Gilbert MR, de Groot JF, Cloughesy TF, S. A, Roberts TM, Zhao JJ, Lee EQ, Nayak L, Heath JR, Horky LL, Batchelor TT, Beroukhim R, Chang SM, Ligon AH, Dunn IF, Koul D, Young GS, Prados MD, Reardon DA, Yung WKA, Ligon KL. Buparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial. Journal Of Clinical Oncology 2019, 37: jco.18.01207. PMID: 30715997, PMCID: PMC6553812, DOI: 10.1200/jco.18.01207.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAminopyridinesAntineoplastic AgentsBrain NeoplasmsChemotherapy, AdjuvantDisease ProgressionEnzyme ActivationFemaleGlioblastomaHumansMaleMiddle AgedMorpholinesNeoadjuvant TherapyNeoplasm Recurrence, LocalPhosphatidylinositol 3-KinasePhosphoinositide-3 Kinase InhibitorsProgression-Free SurvivalTime FactorsConceptsPhase II trialCohort 2Cohort 1PI3K pathwayTumor tissueII trialRecurrent glioblastomaBrain penetrationPan-PI3K inhibitor buparlisibPathway inhibitionPathway activationCommon grade 3K pathwayPrimary end pointGreater adverse eventsProgression-free survivalPI3K pathway inhibitionPI3K pathway activationPlasma drug levelsSingle-agent efficacySignificant brain penetrationPI3K inhibitorsMedian PFSOpen labelAdverse events
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
2014
Phase II Study of Bevacizumab, Temozolomide, and Hypofractionated Stereotactic Radiotherapy for Newly Diagnosed Glioblastoma
Omuro A, Beal K, Gutin P, Karimi S, Correa DD, Kaley TJ, DeAngelis LM, Chan TA, Gavrilovic IT, Nolan C, Hormigo A, Lassman AB, Mellinghoff I, Grommes C, Reiner AS, Panageas KS, Baser RE, Tabar V, Pentsova E, Sanchez J, Barradas-Panchal R, Zhang J, Faivre G, Brennan CW, Abrey LE, Huse JT. Phase II Study of Bevacizumab, Temozolomide, and Hypofractionated Stereotactic Radiotherapy for Newly Diagnosed Glioblastoma. Clinical Cancer Research 2014, 20: 5023-5031. PMID: 25107913, PMCID: PMC4523080, DOI: 10.1158/1078-0432.ccr-14-0822.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBiopsyBrain NeoplasmsChemotherapy, AdjuvantCombined Modality TherapyDacarbazineFemaleGlioblastomaHumansMagnetic Resonance ImagingMaleMiddle AgedRadiosurgeryTemozolomideTreatment OutcomeYoung AdultConceptsObjective response rateOverall survivalRadiotherapy schedulesMedian overall survivalPhase II studyHypofractionated Stereotactic RadiotherapyPhase II trialApparent diffusion coefficient ratioRelative cerebral blood volumeDynamic susceptibility contrast perfusion MRICerebral blood volumeNeuropsychological test scoresMedian PFSPersistent hypermetabolismAdjuvant temozolomidePrimary endpointII studyII trialPoor OSStandard dosesFDG-PETPrognostic valuePoor prognosisHistorical controlsTumor volume
2008
Adjuvant dibromodulcitol and BCNU chemotherapy in anaplastic astrocytoma: Results of a randomised European Organisation for Research and Treatment of Cancer phase III study (EORTC study 26882)
Hildebrand J, Gorlia T, Kros JM, Afra D, Frenay M, Omuro A, Stupp R, Lacombe D, Allgeier A, van den Bent MJ, investigators O. Adjuvant dibromodulcitol and BCNU chemotherapy in anaplastic astrocytoma: Results of a randomised European Organisation for Research and Treatment of Cancer phase III study (EORTC study 26882). European Journal Of Cancer 2008, 44: 1210-1216. PMID: 18248979, DOI: 10.1016/j.ejca.2007.12.005.Peer-Reviewed Original ResearchConceptsProgression-free survivalCentral pathology reviewOverall survivalAnaplastic astrocytomaMonths 95Pathology reviewAA patientsGlioblastoma multiformeConfidence intervalsPrevious phase III trialsMedian overall survivalPhase III studyPhase III trialsGrade 3 tumorsLonger overall survivalTotal treatment durationAdjuvant chemotherapyEORTC studyAdjuvant regimenIII studyIII trialsImproved survivalTreat analysisPathological assessmentBCNU chemotherapy