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 factorGlutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo
Venneti S, Dunphy MP, Zhang H, Pitter KL, Zanzonico P, Campos C, Carlin SD, La Rocca G, Lyashchenko S, Ploessl K, Rohle D, Omuro AM, Cross JR, Brennan CW, Weber WA, Holland EC, Mellinghoff IK, Kung HF, Lewis JS, Thompson CB. Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo. Science Translational Medicine 2015, 7: 274ra17. PMID: 25673762, PMCID: PMC4431550, DOI: 10.1126/scitranslmed.aaa1009.Peer-Reviewed Original ResearchConceptsPositron emission tomographyPermeable blood-brain barrierChemo/radiation therapyHigh tumor/background ratiosClear tumor delineationDecreased tumor burdenHigh background uptakeTumor/background ratiosBlood-brain barrierAltered glucose metabolismHuman glioma patientsVivo positron emission tomographyProgressive diseaseTumor burdenMetabolic evaluationBrain uptakeClinical managementTumor avidityGlioma patientsRadiation therapyGlucose metabolismBackground uptakeEmission tomographyGliomasCancer cellsR-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma
Omuro A, Correa DD, DeAngelis LM, Moskowitz CH, Matasar MJ, Kaley TJ, Gavrilovic IT, Nolan C, Pentsova E, Grommes CC, Panageas KS, Baser RE, Faivre G, Abrey LE, Sauter CS. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood 2015, 125: 1403-1410. PMID: 25568347, PMCID: PMC4342354, DOI: 10.1182/blood-2014-10-604561.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAntibodies, Monoclonal, Murine-DerivedAntineoplastic Combined Chemotherapy ProtocolsBusulfanCentral Nervous System NeoplasmsCombined Modality TherapyCyclophosphamideCytarabineFemaleFollow-Up StudiesHematopoietic Stem Cell TransplantationHumansLymphoma, Non-HodgkinMaleMethotrexateMiddle AgedNeoplasm GradingNeoplasm StagingProcarbazinePrognosisRituximabSurvival RateThiotepaTransplantation, AutologousVincristineYoung AdultConceptsAutologous stem cell transplantProgression-free survivalHigh-dose chemotherapyPrimary central nervous system lymphomaStem cell transplantOverall survivalR-MPVHigh-dose methotrexate-based chemotherapyTwo-year progression-free survivalConsolidation high-dose chemotherapyMedian progression-free survivalCentral nervous system lymphomaMedian Karnofsky performance status 80Treatment-related deathsTwo-year OSCycles of chemotherapyMethotrexate-based chemotherapyObjective response ratePrimary end pointAcceptable toxicity profileMainstay of treatmentPhase 2 studyPrimary CNS lymphomaNervous system lymphomaBlood-brain barrier
2014
Emerging Therapies for Glioblastoma
Thomas AA, Brennan CW, DeAngelis LM, Omuro AM. Emerging Therapies for Glioblastoma. JAMA Neurology 2014, 71: 1437-1444. PMID: 25244650, DOI: 10.1001/jamaneurol.2014.1701.Peer-Reviewed Original ResearchConceptsClinical trialsCommon primary malignant brain tumorPrimary malignant brain tumorCancer stemlike cellsInnovative clinical trialsBlood-brain barrierMalignant brain tumorsPatient-tailored treatmentNew radiotherapy techniquesHeterogeneous molecular featuresImmune system interactionsGrowth factor receptorTerms glioblastomaMedian survivalDisease courseImmune checkpointsTemozolomide chemotherapyMultimodal treatmentPatient enrollmentAggressive tumorsTreatment advancesBrain neoplasmsDrug exposureBrain microenvironmentMalignant gliomas
2011
A phase II study of the Ras-MAPK signaling pathway inhibitor TLN-4601 in patients with glioblastoma at first progression
Mason WP, Belanger K, Nicholas G, Vallières I, Mathieu D, Kavan P, Desjardins A, Omuro A, Reymond D. A phase II study of the Ras-MAPK signaling pathway inhibitor TLN-4601 in patients with glioblastoma at first progression. Journal Of Neuro-Oncology 2011, 107: 343-349. PMID: 22048878, DOI: 10.1007/s11060-011-0747-6.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsBrain NeoplasmsChromatography, LiquidDibenzazepinesErbB ReceptorsFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticGlioblastomaHumansInfusions, IntraventricularKaplan-Meier EstimateMagnetic Resonance ImagingMaleMiddle AgedPTEN PhosphohydrolaseTandem Mass SpectrometryConceptsPharmacokinetic evaluationProgressive glioblastomaFirst progressionM2/dayPhase II studyMR scansPhase II trialContinuous intravenous administrationBlood-brain barrierLack of efficacyPeripheral benzodiazepine receptorEvaluable patientsStable diseaseII trialRadiographic progressionAdverse eventsII studyRecurrent glioblastomaDisease progressionDrug levelsIntravenous administrationBiomarker assessmentPatientsAnimal modelsBenzodiazepine receptors
2007
A phase II trial of temozolomide and vinorelbine for patients with recurrent brain metastases
Iwamoto F, Omuro A, Raizer J, Nolan C, Hormigo A, Lassman A, Gavrilovic I, Abrey L. A phase II trial of temozolomide and vinorelbine for patients with recurrent brain metastases. Journal Of Clinical Oncology 2007, 25: 2050-2050. DOI: 10.1200/jco.2007.25.18_suppl.2050.Peer-Reviewed Original ResearchPhase II trialRecurrent brain metastasesObjective radiographic responseBrain metastasesII trialRadiographic responseResponse rateWhole-brain radiation therapyAdequate organ functionBrain metastasis resectionSingle-agent temozolomideGrade 3/4 toxicitiesPhase I trialPhase II componentPopulation of patientsFavorable toxicity profileBlood-brain barrierPrimary tumor siteHead/neckTwo-stage clinical trialAssessable patientsMedian KPSMedian PFSPrior therapyMetastasis resection