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
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
2014
AT-47PHASE I TRIAL OF INTRATHECAL TRASTUZUMAB IN HER2 POSITIVE LEPTOMENINGEAL METASTASES
Raizer J, Pentsova E, Omuro A, Lin N, Nayak L, Quant E, Kumthekar P. AT-47PHASE I TRIAL OF INTRATHECAL TRASTUZUMAB IN HER2 POSITIVE LEPTOMENINGEAL METASTASES. Neuro-Oncology 2014, 16: v19-v19. PMCID: PMC4217826, DOI: 10.1093/neuonc/nou237.46.Peer-Reviewed Original ResearchHER2-positive breast cancerPositive breast cancerLeptomeningeal metastasesDose levelsBreast cancerIntrathecal trastuzumabCentral nervous system penetrationPhase I clinical trialPhase II studyHumanized monoclonal antibodyIT trastuzumabMedian KPSII studyProgressive diseaseI trialMedian ageOmmaya reservoirCSF levelsAnaplastic ependymomaClinical trialsPatientsPK dataTherapeutic levelsIts TreatmentTrastuzumabNI-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
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