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
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
2015
Phase I Study of Single Agent Ibrutinib in Recurrent/Refractory Primary and Secondary CNS Lymphoma
Christian G, Thomas K, Abdel-Wahab O, Omuro A, Ingo M, DeAngelis L. Phase I Study of Single Agent Ibrutinib in Recurrent/Refractory Primary and Secondary CNS Lymphoma. Blood 2015, 126: 3960. DOI: 10.1182/blood.v126.23.3960.3960.Peer-Reviewed Original ResearchRefractory primary CNS lymphomaPrimary CNS lymphomaSecondary CNS lymphomaDose level 2CNS lymphomaCommon grade 2 toxicityRecurrent primary CNS lymphomaRecurrent/refractory diseaseAggressive primary brain tumorCD20 antibody therapyCNS lymphoma patientsDose of ibrutinibGrade 4 toxicityPrior treatment regimensDose level 1Grade 2 toxicityGrade 3 toxicityMethotrexate-based chemotherapyEnd-organ functionNormal end-organ functionSingle-agent ibrutinibPhase I trialPrimary brain tumorsPromising clinical responsesAlternative therapeutic approach
2014
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
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 tumors
2013
Phase 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 arrest
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
2006
Vinorelbine combined with a protracted course of temozolomide for recurrent brain Metastases: a phase I trial
Omuro AM, Raizer JJ, Demopoulos A, Malkin MG, Abrey LE. Vinorelbine combined with a protracted course of temozolomide for recurrent brain Metastases: a phase I trial. Journal Of Neuro-Oncology 2006, 78: 277-280. PMID: 16614943, DOI: 10.1007/s11060-005-9095-8.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, AlkylatingAntineoplastic Agents, PhytogenicAntineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsBreast NeoplasmsCarcinoma, Non-Small-Cell LungDacarbazineDisease-Free SurvivalDose-Response Relationship, DrugDrug Administration ScheduleFemaleHumansLung NeoplasmsLymphopeniaMaleMaximum Tolerated DoseMiddle AgedNeutropeniaTemozolomideThrombocytopeniaTreatment OutcomeVinblastineVinorelbineConceptsCourses of temozolomideRecurrent brain metastasesBrain metastasesDose of vinorelbineProgressive brain metastasesPhase II trialPhase I trialEfficacy of temozolomideVinorelbine doseII trialStarting doseMedian survivalRadiographic responseI trialMedian ageModest efficacyNew regimenPatient 2Lung cancerPrimary tumorGrade 3PatientsVinorelbineTemozolomideDose