2022
Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter
Lim M, Weller M, Idbaih A, Steinbach J, Finocchiaro G, Raval RR, Ansstas G, Baehring J, Taylor JW, Honnorat J, Petrecca K, De Vos F, Wick A, Sumrall A, Sahebjam S, Mellinghoff IK, Kinoshita M, Roberts M, Slepetis R, Warad D, Leung D, Lee M, Reardon DA, Omuro A. Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro-Oncology 2022, 24: 1935-1949. PMID: 35511454, PMCID: PMC9629431, DOI: 10.1093/neuonc/noac116.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survivalMGMT promoterBaseline corticosteroidsTreatment-related adverse event ratesImmune checkpoint inhibitor nivolumabNew safety signalsPhase III trialsAdverse event ratesCheckpoint inhibitor nivolumabCare radiotherapyInhibitor nivolumabPrimary endpointIII trialsSame regimenExperience recurrenceNivolumabSafety signalsPlaceboPatientsRadiotherapyTemozolomideEvent ratesMonthsPhase III
2019
Residual Tumor Volume, Cell Volume Fraction, and Tumor Cell Kill During Fractionated Chemoradiation Therapy of Human Glioblastoma using Quantitative Sodium MR Imaging
Thulborn KR, Lu A, Atkinson IC, Pauliah M, Beal K, Chan TA, Omuro A, Yamada J, Bradbury MS. Residual Tumor Volume, Cell Volume Fraction, and Tumor Cell Kill During Fractionated Chemoradiation Therapy of Human Glioblastoma using Quantitative Sodium MR Imaging. Clinical Cancer Research 2019, 25: 1226-1232. PMID: 30487127, PMCID: PMC7462306, DOI: 10.1158/1078-0432.ccr-18-2079.Peer-Reviewed Original ResearchConceptsResidual tumor volumeTumor cell killTissue sodium concentrationChemoradiation therapyOverall survivalHuman glioblastomaTumor volumeQuantitative sodium MR imagingCell killQuantitative sodium MRITumor cellsVariable tumor responseSodium MRITwo-compartment modelTumor resectionTumor responseDisease progressionSodium MR imagingTumor marginsMR imagingTherapyGlioblastomaTreatment volumeCancer cellsSodium concentration
2018
Multicenter Phase IB Trial of Carboxyamidotriazole Orotate and Temozolomide for Recurrent and Newly Diagnosed Glioblastoma and Other Anaplastic Gliomas.
Omuro A, Beal K, McNeill K, Young RJ, Thomas A, Lin X, Terziev R, Kaley TJ, DeAngelis LM, Daras M, Gavrilovic IT, Mellinghoff I, Diamond EL, McKeown A, Manne M, Caterfino A, Patel K, Bavisotto L, Gorman G, Lamson M, Gutin P, Tabar V, Chakravarty D, Chan TA, Brennan CW, Garrett-Mayer E, Karmali RA, Pentsova E. Multicenter Phase IB Trial of Carboxyamidotriazole Orotate and Temozolomide for Recurrent and Newly Diagnosed Glioblastoma and Other Anaplastic Gliomas. Journal Of Clinical Oncology 2018, 36: 1702-1709. PMID: 29683790, PMCID: PMC5993168, DOI: 10.1200/jco.2017.76.9992.Peer-Reviewed Original ResearchConceptsAnaplastic gliomasCohort 2Cohort 1Median progression-free survivalFavorable brain penetrationMedian overall survivalPhase Ib studyPhase Ib trialPhase II doseProgression-free survivalRecurrent anaplastic gliomasDependent calcium channelsNovel oral inhibitorSignal of activityMismatch repair genesIb trialTreat populationMethylguanine-DNA methyltransferaseOverall survivalComplete responseFlat doseOral inhibitorBrain penetrationResults FortyTherapeutic concentrations
2017
Multicenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma
Thomas AA, Abrey LE, Terziev R, Raizer J, Martinez NL, Forsyth P, Paleologos N, Matasar M, Sauter CS, Moskowitz C, Nimer SD, DeAngelis LM, Kaley T, Grimm S, Louis DN, Cairncross JG, Panageas KS, Briggs S, Faivre G, Mohile NA, Mehta J, Jonsson P, Chakravarty D, Gao J, Schultz N, Brennan CW, Huse JT, Omuro A. Multicenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma. Neuro-Oncology 2017, 19: 1380-1390. PMID: 28472509, PMCID: PMC5596171, DOI: 10.1093/neuonc/nox086.Peer-Reviewed Original ResearchConceptsAutologous stem cell transplantProgression-free survivalHigh-dose chemotherapyStem cell transplantAnaplastic oligodendrogliomaAnaplastic oligoastrocytomaHDC-ASCTMulticenter phase II studyMyeloablative high-dose chemotherapyChemotherapy-based approachesCycles of temozolomideOverall survival 93Phase II studyRadiation-related toxicityUnexpected adverse eventsNext-generation sequencingChemotherapy-sensitive tumorsWide molecular heterogeneityToxic deathsAdverse eventsII studyMyeloablative chemotherapyProspective trialIntact patientsCell transplant
2016
Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial
Xu R, Shimizu F, Hovinga K, Beal K, Karimi S, Droms L, Peck KK, Gutin P, Iorgulescu JB, Kaley T, DeAngelis L, Pentsova E, Nolan C, Grommes C, Chan T, Bobrow D, Hormigo A, Cross JR, Wu N, Takebe N, Panageas K, Ivy P, Supko JG, Tabar V, Omuro A. Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial. Clinical Cancer Research 2016, 22: 4786-4796. PMID: 27154916, PMCID: PMC5050072, DOI: 10.1158/1078-0432.ccr-16-0048.Peer-Reviewed Original ResearchConceptsRecurrent tumorsCancer-initiating cell populationGamma secretase inhibitor RO4929097Blood-brain barrier disruptionBlood-brain barrier penetrationDose-limiting toxicityNotch intracellular domainPotential therapeutic optionSignificant decreaseRelative plasma volumeHigh-grade gliomasTumor explant culturesNotch pathwayI trialDismal prognosisTherapeutic optionsBarrier disruptionDrug exposureAnaplastic astrocytomaAngiogenic factorsTumor tissueAntiangiogenic roleTarget modulationDrug penetrationPerfusion MRI
2013
Rituximab, Methotrexate, Procarbazine, and Vincristine Followed by Consolidation Reduced-Dose Whole-Brain Radiotherapy and Cytarabine in Newly Diagnosed Primary CNS Lymphoma: Final Results and Long-Term Outcome
Morris PG, Correa DD, Yahalom J, Raizer JJ, Schiff D, Grant B, Grimm S, Lai RK, Reiner AS, Panageas K, Karimi S, Curry R, Shah G, Abrey LE, DeAngelis LM, Omuro A. Rituximab, Methotrexate, Procarbazine, and Vincristine Followed by Consolidation Reduced-Dose Whole-Brain Radiotherapy and Cytarabine in Newly Diagnosed Primary CNS Lymphoma: Final Results and Long-Term Outcome. Journal Of Clinical Oncology 2013, 31: 3971-3979. PMID: 24101038, PMCID: PMC5569679, DOI: 10.1200/jco.2013.50.4910.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, Murine-DerivedAntineoplastic Combined Chemotherapy ProtocolsCentral Nervous System NeoplasmsChemoradiotherapyCranial IrradiationCytarabineDisease-Free SurvivalFemaleHumansLymphomaMaleMethotrexateMiddle AgedProcarbazineRituximabTimeTreatment OutcomeVincristineConceptsProgression-free survivalMedian progression-free survivalMedian overall survivalPrimary CNS lymphomaOverall survivalR-MPVComplete responseCNS lymphomaMedian Karnofsky performance scoreMulticenter phase II studyLong-term disease controlEnd pointApparent diffusion coefficientExploratory end pointsKarnofsky performance scorePhase II studyPrimary end pointWhole brain radiotherapyLong-term outcomesWhite matter changesHigh response rateInduction chemotherapyStandard WBRTBrain radiotherapyII study