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
2018
Radiographic patterns of recurrence and pathologic correlation in malignant gliomas treated with bevacizumab
Thomas A, Rosenblum M, Karimi S, DeAngelis LM, Omuro A, Kaley TJ. Radiographic patterns of recurrence and pathologic correlation in malignant gliomas treated with bevacizumab. CNS Oncology 2018, 07: 7-13. PMID: 29388793, PMCID: PMC6001559, DOI: 10.2217/cns-2017-0025.Peer-Reviewed Original ResearchConceptsMalignant gliomasRecurrence patternsDiffusion-weighted imaging abnormalitiesDiffusion-weighted imagingStandard clinical settingMG patientsImaging abnormalitiesMRI abnormalitiesPathologic findingsTumor recurrenceRadiographic patternsPathologic correlationBevacizumabClinical settingNecrosisPatientsRecurrenceRecent reportsTumorsGliomasAbnormalitiesLeptomeningealSurgery
2016
Multicenter Phase IB trial of carboxyamidotriazole orotate (CTO) combined with temozolomide (TMZ) for recurrent glioblastoma (GBM) and other malignant gliomas (MG).
Lin X, Kaley T, Pentsova E, DeAngelis L, Daras M, Gavrilovic I, Mellinghoff I, McKeown A, Manne M, Hansen J, Bavisotto L, Gorman G, Lamson M, Karmali R, Omuro A. Multicenter Phase IB trial of carboxyamidotriazole orotate (CTO) combined with temozolomide (TMZ) for recurrent glioblastoma (GBM) and other malignant gliomas (MG). Journal Of Clinical Oncology 2016, 34: 2064-2064. DOI: 10.1200/jco.2016.34.15_suppl.2064.Peer-Reviewed Original Research
2015
Multicenter Phase I Dose Escalation Study of Hypofractionated Stereotactic Radiotherapy with Bevacizumab in the Treatment of Recurrent Malignant Glioma (S43.005)
Neil E, Clarke J, Beal K, Gutin P, Igor B, Kaley T, Lassman A, Perezic-Mustafa M, Young R, Omuro A. Multicenter Phase I Dose Escalation Study of Hypofractionated Stereotactic Radiotherapy with Bevacizumab in the Treatment of Recurrent Malignant Glioma (S43.005). Neurology 2015, 84 DOI: 10.1212/wnl.84.14_supplement.s43.005.Peer-Reviewed Original Research
2014
AT-35INTERMITTENT HIGH DOSE (PULSATILE) ERLOTINIB FOR EGFRvIII MUTANT RECURRENT MALIGNANT GLIOMAS: A PILOT CLINICAL TRIAL
Lassman A, Grommes C, Panageas K, Iwamoto F, DeAngelis L, Kaley T, Gavrilovic I, Pentsova E, Omuro A, Corpuz C, Briggs S, Otap D, Qin W, Cross J, Mellinghoff I. AT-35INTERMITTENT HIGH DOSE (PULSATILE) ERLOTINIB FOR EGFRvIII MUTANT RECURRENT MALIGNANT GLIOMAS: A PILOT CLINICAL TRIAL. Neuro-Oncology 2014, 16: v16-v16. PMCID: PMC4217814, DOI: 10.1093/neuonc/nou237.35.Peer-Reviewed Original ResearchRecurrent malignant gliomaMalignant gliomasInhibitor therapyHigh-dose erlotinibOngoing complete responseEGFR-TKI erlotinibPopulation of patientsMedian age 58Pilot clinical trialInadequate drug deliveryKinase inhibitor therapyDose erlotinibEligible patientsPulsatile dosingAdverse eventsMedian survivalComplete responseDaily doseTKI erlotinibMedian CmaxAnaplastic gliomasClinical trialsAge 58Surgical armLimited efficacyNI-57DYNAMIC CONTRAST-ENHANCED MAGNETIC RESONANCE PERFUSION WEIGHTED IMAGING (DCE-MRI) AND DIFFUSION WEIGHTED IMAGING (DWI) FOR PHARMACODYNAMIC EVALUATION OF CARBOXYAMIDOTRIAZOLE OROTATE (CTO) AND TEMOZOLOMIDE IN MALIGNANT GLIOMA
Magge R, Perez J, Young R, Kaley T, Pentsova E, DeAngelis L, Diamond E, Mellinghoff I, Peck K, Anderson B, Gorman G, Mclean S, Karmali R, Omuro A. NI-57DYNAMIC CONTRAST-ENHANCED MAGNETIC RESONANCE PERFUSION WEIGHTED IMAGING (DCE-MRI) AND DIFFUSION WEIGHTED IMAGING (DWI) FOR PHARMACODYNAMIC EVALUATION OF CARBOXYAMIDOTRIAZOLE OROTATE (CTO) AND TEMOZOLOMIDE IN MALIGNANT GLIOMA. Neuro-Oncology 2014, 16: v150-v151. PMCID: PMC4218384, DOI: 10.1093/neuonc/nou264.55.Peer-Reviewed Original ResearchBlood perfusionMalignant gliomasVascular permeabilityDCE-MRIProgressive malignant gliomaPhase I trialSubset of patientsContrast-Enhanced Magnetic ResonanceWnt/b-cateninMann-Whitney U testEarly pharmacodynamic effectsVolumetric histogram analysisMechanism of actionBiological effectsAdvanced imaging techniquesI trialOral inhibitorEarly drug developmentPharmacodynamic effectsVascular permeability parametersDrug exposurePharmacodynamic evaluationVEGF blockadeAdvanced neuroimagingBrain tumorsEmerging 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 gliomasPhase IB trial of carboxyamidotriazole orotate (CTO) and temozolomide for recurrent malignant glioma (MG): A novel mechanism for modulation of multiple oncogenic pathways.
Omuro A, Kaley T, Pentsova E, DeAngelis L, Urba W, Taylor M, Anderson B, Gorman G, McLean S, Karmali R. Phase IB trial of carboxyamidotriazole orotate (CTO) and temozolomide for recurrent malignant glioma (MG): A novel mechanism for modulation of multiple oncogenic pathways. Journal Of Clinical Oncology 2014, 32: 2071-2071. DOI: 10.1200/jco.2014.32.15_suppl.2071.Peer-Reviewed Original Research
2013
Glioblastoma and Other Malignant Gliomas: A Clinical Review
Omuro A, DeAngelis LM. Glioblastoma and Other Malignant Gliomas: A Clinical Review. JAMA 2013, 310: 1842-1850. PMID: 24193082, DOI: 10.1001/jama.2013.280319.Peer-Reviewed Original ResearchConceptsMalignant gliomasRisk factorsAmerican Heart Association classification systemCommon primary malignant brain tumorPrimary malignant brain tumorGrade III tumorsStandard of careSpecific antitumor therapyMalignant brain tumorsAuthors' own filesFrequent clinical complicationEnvironmental risk factorsCertain genetic syndromesOwn filesTerms glioblastomaThromboembolic eventsCommon complicationNeurologic symptomsOverall prognosisAnnual incidenceDismal prognosisSymptom managementClinical reviewTherapeutic optionsClinical complicationsPhase I trial of temsirolimus (TEM) and perifosine (PER) for recurrent or progressive malignant glioma (MG).
Kaley T, Pentsova E, Omuro A, Mellinghoff I, Nolan C, Gavrilovic I, DeAngelis L, Lacouture M, Holland E, Lassman A. Phase I trial of temsirolimus (TEM) and perifosine (PER) for recurrent or progressive malignant glioma (MG). Journal Of Clinical Oncology 2013, 31: 2095-2095. DOI: 10.1200/jco.2013.31.15_suppl.2095.Peer-Reviewed Original ResearchRecurrent malignant gliomaPhase I trialMalignant gliomasI trialDose level 3Dose level 7Dose of temsirolimusMedian age 52Progressive malignant gliomaSynergistic anti-tumor effectPI3K/Akt/mTOR signalingAkt/mTOR SignalingMTOR inhibitor temsirolimusAnti-tumor effectsPotential therapeutic targetKPS 80Prior RTPrior therapyLimiting toxicitiesIntracerebral hemorrhageCombined therapyCombination therapyPreclinical dataLung infectionCell cycle arrestA phase I study of carboxyamidotriazole orotate (CTO) in of advanced solid tumors.
Sandler A, Taylor M, Urba W, Omuro A, Anderson B, Hansen D, Fisher B, Claeys A, Greathouse A, McLean S, Karmali R. A phase I study of carboxyamidotriazole orotate (CTO) in of advanced solid tumors. Journal Of Clinical Oncology 2013, 31: 2518-2518. DOI: 10.1200/jco.2013.31.15_suppl.2518.Peer-Reviewed Original ResearchAdvanced solid tumorsCell lung cancerStable diseaseLung cancerSolid tumorsSquamous cell lung cancerSmall cell lung cancerAdequate organ functionGrade 3 fatigueCreatine kinase elevationSquamous cell carcinomaColon tumor xenograftsAnti-tumor effectsAnti-invasive propertiesPharmacokinetic samplingAdverse eventsQTc prolongationCell carcinomaTumor responseEGFR mutationsPIK3CA mutationsMalignant gliomasLung adenocarcinomaTumor assessmentCT scan
2012
Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma
Omuro A, Chan TA, Abrey LE, Khasraw M, Reiner AS, Kaley TJ, Deangelis LM, Lassman AB, Nolan CP, Gavrilovic IT, Hormigo A, Salvant C, Heguy A, Kaufman A, Huse JT, Panageas KS, Hottinger AF, Mellinghoff I. Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma. Neuro-Oncology 2012, 15: 242-250. PMID: 23243055, PMCID: PMC3548585, DOI: 10.1093/neuonc/nos295.Peer-Reviewed Original ResearchConceptsKarnofsky performance scoreProgression-free survival ratesBevacizumab-naive patientsRecurrent malignant gliomaPhase II trialMalignant gliomasII trialPrimary endpointSurvival rateContinuous low-dose temozolomideMedian Karnofsky performance scoreLow Karnofsky performance scoreAdvanced malignant gliomaLow-dose temozolomideMedian overall survivalHalf of patientsFurther treatment strategiesMutations of EGFRBevacizumab exposureEligible patientsTemozolomide schedulesMG patientsOverall survivalMedian ageClinical benefit
2011
Targeted Therapy for Malignant Gliomas
Dankwah-Quansah M, Omuro A. Targeted Therapy for Malignant Gliomas. Tumors Of The Central Nervous System 2011, 299-307. DOI: 10.1007/978-94-007-0344-5_31.Peer-Reviewed Original ResearchMalignant gliomasAggressive primary brain tumorFatal disease outcomeSingle-agent trialsSingle-agent treatmentPrimary brain tumorsAkt/mTORDevelopment of combinationsAgent trialsDismal prognosisPatient selectionStandard treatmentTargeted therapyDisease outcomeAnaplastic astrocytomaAnaplastic oligodendrogliomaBrain tumorsTherapy trialsNew treatmentsPathway inhibitionGliomasAgent treatmentTrialsRas/MAPKPromising activity
2010
Phase II trial of continuous low-dose temozolomide (TMZ) for recurrent malignant glioma (MG) with and without prior exposure to bevacizumab (BEV).
Khasraw M, Abrey L, Lassman A, Hormigo A, Nolan C, Gavrilovic I, Mellinghoff I, Reiner A, DeAngelis L, Omuro A. Phase II trial of continuous low-dose temozolomide (TMZ) for recurrent malignant glioma (MG) with and without prior exposure to bevacizumab (BEV). Journal Of Clinical Oncology 2010, 28: 2065-2065. DOI: 10.1200/jco.2010.28.15_suppl.2065.Peer-Reviewed Original ResearchA phase I safety and pharmacokinetic study of XL765 (SAR245409), a novel PI3K/TORC1/TORC2 inhibitor, in combination with temozolomide (TMZ) in patients (pts) with newly diagnosed malignant glioma.
Nghiemphu P, Omuro A, Cloughesy T, Mellinghoff I, Norden A, Nguyen L, Rajangam K, Wen P. A phase I safety and pharmacokinetic study of XL765 (SAR245409), a novel PI3K/TORC1/TORC2 inhibitor, in combination with temozolomide (TMZ) in patients (pts) with newly diagnosed malignant glioma. Journal Of Clinical Oncology 2010, 28: 3085-3085. DOI: 10.1200/jco.2010.28.15_suppl.3085.Peer-Reviewed Original Research
2009
Antiangiogenic Strategies for the Treatment of Gliomas
Bazzoli E, Omuro A. Antiangiogenic Strategies for the Treatment of Gliomas. 2009, 243-263. DOI: 10.1007/978-1-4419-0410-2_12.Peer-Reviewed Original ResearchMalignant gliomasAntiangiogenic strategiesVascular endothelial growth factor (VEGF) pathwayEndothelial growth factor pathwayNew antiangiogenic treatmentsRecurrent malignant gliomaProgression-free survivalVEGF monoclonal antibodyInitial clinical benefitTreatment of gliomaHigh response rateGrowth factor pathwaysDifferent molecular driversMost patientsSurvival benefitClinical benefitAntiangiogenic treatmentAntiangiogenic drugsAntiangiogenesis treatmentResponse rateSolid tumorsComplex biologic processClinical settingFactor pathwayGliomas
2008
What is the place of bevacizumab and irinotecan in the treatment of glioblastoma and other malignant gliomas?
Omuro AM, Delattre JY. What is the place of bevacizumab and irinotecan in the treatment of glioblastoma and other malignant gliomas? Current Opinion In Neurology 2008, 21: 717-719. PMID: 18989118, DOI: 10.1097/wco.0b013e3283184625.Peer-Reviewed Original ResearchConceptsMalignant gliomasOverall survivalClinical trialsProspective phase II trialPlace of bevacizumabProgression-free survivalPhase II trialNew treatment strategiesHigh response rateTreatment of glioblastomaII trialRecurrent diseaseSalvage treatmentCytotoxic chemotherapyMost patientsConventional radiographic methodsDisease progressionHistorical controlsSurvival resultsRadiographic criteriaTreatment strategiesBevacizumabResponse rateNew treatmentsGliomas
2007
Editorial: what is new in the treatment of gliomas?
Omuro AM, Delattre JY. Editorial: what is new in the treatment of gliomas? Current Opinion In Neurology 2007, 20: 704-707. PMID: 17992093, DOI: 10.1097/wco.0b013e3282f1beef.Peer-Reviewed Original ResearchConceptsTreatment of gliomaTherapeutic decisionsEvidence-based therapeutic decisionsBevacizumab-based combinationsRecurrent malignant gliomaRole of chemotherapyPhase II trialStandard of carePhase III evidenceHigh response ratePhase II resultsSingle positive resultTemozolomide concomitantTemozolomide schedulesII trialSurvival benefitRandomized trialsGrade IIIMalignant gliomasResponse rateGliomasSuch trialsTraditional treatmentTrialsCodeletion statusLessons learned in the development of targeted therapy for malignant gliomas
Omuro AM, Faivre S, Raymond E. Lessons learned in the development of targeted therapy for malignant gliomas. Molecular Cancer Therapeutics 2007, 6: 1909-1919. PMID: 17620423, DOI: 10.1158/1535-7163.mct-07-0047.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factor receptorEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsReceptor tyrosine kinase inhibitorsPreliminary efficacy resultsPrognosis of patientsTranslational researchEndothelial growth factor receptorEffective treatment optionTyrosine kinase inhibitorsGrowth factor receptorRecurrent diseaseRapamycin inhibitorsPreclinical dataStandard treatmentTreatment optionsEfficacy resultsMalignant gliomasSuch tumorsNovel agentsAnaplastic astrocytomaMost trialsTrial designProtein kinase C betaPathway inhibitor