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
Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143
Omuro A, Vlahovic G, Lim M, Sahebjam S, Baehring J, Cloughesy T, Voloschin A, Ramkissoon SH, Ligon KL, Latek R, Zwirtes R, Strauss L, Paliwal P, Harbison CT, Reardon DA, Sampson JH. Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143. Neuro-Oncology 2017, 20: 674-686. PMID: 29106665, PMCID: PMC5892140, DOI: 10.1093/neuonc/nox208.Peer-Reviewed Original ResearchConceptsAdverse eventsRecurrent glioblastomaCommon treatment-related adverse eventsTreatment-related adverse eventsDeath ligand 1 (PD-L1) expressionEffects of nivolumabExploratory efficacy outcomesSafety/tolerabilityFindings merit further investigationLigand 1 expressionCheckMate 143Ipilimumab doseNivolumab monotherapyStable diseaseAlternative regimenEfficacy outcomesRadiographic progressionMost patientsPartial responseNivolumabIpilimumabMerit further investigationPatientsI cohortFurther evaluationMutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients
Zehir A, Benayed R, Shah RH, Syed A, Middha S, Kim HR, Srinivasan P, Gao J, Chakravarty D, Devlin SM, Hellmann MD, Barron DA, Schram AM, Hameed M, Dogan S, Ross DS, Hechtman JF, DeLair DF, Yao J, Mandelker DL, Cheng DT, Chandramohan R, Mohanty AS, Ptashkin RN, Jayakumaran G, Prasad M, Syed MH, Rema AB, Liu ZY, Nafa K, Borsu L, Sadowska J, Casanova J, Bacares R, Kiecka IJ, Razumova A, Son JB, Stewart L, Baldi T, Mullaney KA, Al-Ahmadie H, Vakiani E, Abeshouse AA, Penson AV, Jonsson P, Camacho N, Chang MT, Won HH, Gross BE, Kundra R, Heins ZJ, Chen HW, Phillips S, Zhang H, Wang J, Ochoa A, Wills J, Eubank M, Thomas SB, Gardos SM, Reales DN, Galle J, Durany R, Cambria R, Abida W, Cercek A, Feldman DR, Gounder MM, Hakimi AA, Harding JJ, Iyer G, Janjigian YY, Jordan EJ, Kelly CM, Lowery MA, Morris LGT, Omuro AM, Raj N, Razavi P, Shoushtari AN, Shukla N, Soumerai TE, Varghese AM, Yaeger R, Coleman J, Bochner B, Riely GJ, Saltz LB, Scher HI, Sabbatini PJ, Robson ME, Klimstra DS, Taylor BS, Baselga J, Schultz N, Hyman DM, Arcila ME, Solit DB, Ladanyi M, Berger MF. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nature Medicine 2017, 23: 703-713. PMID: 28481359, PMCID: PMC5461196, DOI: 10.1038/nm.4333.Peer-Reviewed Original ResearchConceptsMemorial Sloan-Kettering Cancer CenterCancer-related genesProspective clinical sequencingAdvanced solid cancersSequencing platformsStructural variantsGenomic landscapeGenomic mutationsDetailed clinical annotationMutational landscapeSequencing resultsNumber alterationsCancer CenterPatient enrollmentClinical trialsMSK-IMPACTMetastatic cancerSolid cancersNew insightsNormal tissuesClinical sequencingCancer therapyPatientsCancerClinical annotation
2015
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 factor
2014
Phase II trial of sunitinib for recurrent and progressive atypical and anaplastic meningioma
Kaley TJ, Wen P, Schiff D, Ligon K, Haidar S, Karimi S, Lassman AB, Nolan CP, DeAngelis LM, Gavrilovic I, Norden A, Drappatz J, Lee EQ, Purow B, Plotkin SR, Batchelor T, Abrey LE, Omuro A. Phase II trial of sunitinib for recurrent and progressive atypical and anaplastic meningioma. Neuro-Oncology 2014, 17: 116-121. PMID: 25100872, PMCID: PMC4483051, DOI: 10.1093/neuonc/nou148.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factor receptorPhase II trialWorld Health OrganizationGrowth factor receptorII trialPrimary endpointOverall survivalExploratory cohortIntratumoral hemorrhageGrade 3Small molecule tyrosine kinase inhibitorsSingle-arm phase II trialMalignant meningioma patientsRadiographic response rateMedian overall survivalEffective medical therapyProgression-free survivalFactor receptorEndothelial growth factor receptorPlatelet-derived growth factor receptorTyrosine kinase inhibitorsExpression of VEGFR2MR perfusion imagingHigh-grade meningiomasMedian PFSPretreatment Dynamic Susceptibility Contrast MRI Perfusion in Glioblastoma: Prediction of EGFR Gene Amplification
Gupta A, Young R, Shah A, Schweitzer A, Graber J, Shi W, Zhang Z, Huse J, Omuro A. Pretreatment Dynamic Susceptibility Contrast MRI Perfusion in Glioblastoma: Prediction of EGFR Gene Amplification. Clinical Neuroradiology 2014, 25: 143-150. PMID: 24474262, PMCID: PMC4712066, DOI: 10.1007/s00062-014-0289-3.Peer-Reviewed Original Research
2011
Prophylactic intrathecal chemotherapy in primary CNS lymphoma
Sierra del Rio M, Ricard D, Houillier C, Navarro S, Gonzalez-Aguilar A, Idbaih A, Kaloshi G, Elhallani S, Omuro A, Choquet S, Soussain C, Hoang-Xuan K. Prophylactic intrathecal chemotherapy in primary CNS lymphoma. Journal Of Neuro-Oncology 2011, 106: 143-146. PMID: 21739169, DOI: 10.1007/s11060-011-0649-7.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAntimetabolites, AntineoplasticAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsCentral Nervous System NeoplasmsCohort StudiesDisease-Free SurvivalFemaleFollow-Up StudiesHumansInjections, SpinalKarnofsky Performance StatusLomustineLymphomaMaleMethotrexateMethylprednisoloneMiddle AgedNeoplasm Recurrence, LocalNeuroprotective AgentsProcarbazineRetrospective StudiesYoung AdultConceptsPrimary central nervous system lymphomaCentral nervous system lymphomaNervous system lymphomaProphylactic intrathecal chemotherapyIntrathecal chemotherapySystem lymphomaIntrathecal prophylaxisHigh-dose intravenous methotrexateRetrospective single-center studyObjective response ratePatterns of relapsePrimary CNS lymphomaProgression-free survivalSingle-center studyHigh intravenous dosesIntrathecal chemoprophylaxisIntravenous methotrexateProphylaxis withdrawalChemotherapy regimenCNS lymphomaSystemic chemotherapyKarnofsky indexOverall survivalIntravenous dosesMedian age
2005
High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to gefitinib
Omuro AM, Kris MG, Miller VA, Franceschi E, Shah N, Milton DT, Abrey LE. High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to gefitinib. Cancer 2005, 103: 2344-2348. PMID: 15844174, DOI: 10.1002/cncr.21033.Peer-Reviewed Original ResearchConceptsNonsmall cell lung carcinomaCentral nervous systemDisease recurrenceLong-term outcomesCell lung carcinomaBrain metastasesCNS metastasesLeptomeningeal metastasesLung carcinomaHigh incidenceAdvanced nonsmall cell lung carcinomaEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsMedian Karnofsky performance scoreMemorial Sloan-Kettering Cancer CenterMedian overall survival periodReceptor tyrosine kinase inhibitorsInitial disease recurrenceKarnofsky performance scoreOverall survival periodInitial responseTyrosine kinase inhibitorsInitial siteNeurologic symptomsPartial response