2019
Buparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial
Wen PY, Touat M, Alexander BM, Mellinghoff IK, Ramkissoon S, McCluskey CS, Pelton K, Haidar S, Basu SS, Gaffey SC, Brown LE, Martinez-Ledesma JE, Wu S, Kim J, Wei W, Park MA, Huse JT, Kuhn JG, Rinne ML, Colman H, Agar NYR, Omuro AM, DeAngelis LM, Gilbert MR, de Groot JF, Cloughesy TF, S. A, Roberts TM, Zhao JJ, Lee EQ, Nayak L, Heath JR, Horky LL, Batchelor TT, Beroukhim R, Chang SM, Ligon AH, Dunn IF, Koul D, Young GS, Prados MD, Reardon DA, Yung WKA, Ligon KL. Buparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial. Journal Of Clinical Oncology 2019, 37: jco.18.01207. PMID: 30715997, PMCID: PMC6553812, DOI: 10.1200/jco.18.01207.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAminopyridinesAntineoplastic AgentsBrain NeoplasmsChemotherapy, AdjuvantDisease ProgressionEnzyme ActivationFemaleGlioblastomaHumansMaleMiddle AgedMorpholinesNeoadjuvant TherapyNeoplasm Recurrence, LocalPhosphatidylinositol 3-KinasePhosphoinositide-3 Kinase InhibitorsProgression-Free SurvivalTime FactorsConceptsPhase II trialCohort 2Cohort 1PI3K pathwayTumor tissueII trialRecurrent glioblastomaBrain penetrationPan-PI3K inhibitor buparlisibPathway inhibitionPathway activationCommon grade 3K pathwayPrimary end pointGreater adverse eventsProgression-free survivalPI3K pathway inhibitionPI3K pathway activationPlasma drug levelsSingle-agent efficacySignificant brain penetrationPI3K inhibitorsMedian PFSOpen labelAdverse events
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 MRIEvaluating Cancer of the Central Nervous System Through Next-Generation Sequencing of Cerebrospinal Fluid
Pentsova EI, Shah RH, Tang J, Boire A, You D, Briggs S, Omuro A, Lin X, Fleisher M, Grommes C, Panageas KS, Meng F, Selcuklu SD, Ogilvie S, Distefano N, Shagabayeva L, Rosenblum M, DeAngelis LM, Viale A, Mellinghoff IK, Berger MF. Evaluating Cancer of the Central Nervous System Through Next-Generation Sequencing of Cerebrospinal Fluid. Journal Of Clinical Oncology 2016, 34: 2404-2415. PMID: 27161972, PMCID: PMC4981784, DOI: 10.1200/jco.2016.66.6487.Peer-Reviewed Original ResearchConceptsCentral nervous systemPrimary brain tumorsCerebrospinal fluidCell-free DNACNS involvementBrain tumorsNervous systemCommon malignant primary brain tumorMalignant primary brain tumorRoutine lumbar punctureRelevant genomic alterationsCNS metastasesCNS cancersLumbar punctureCancer-associated genesTumor disseminationHarbored mutationsPatientsTumor evolutionSolid tumorsTumor progressionTumor tissueCancerLiquid biopsyTumors
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
2013
Tumor pharmacokinetics (PK) and pharmacodynamics (PD) of SAR245409 (XL765) and SAR245408 (XL147) administered as single agents to patients with recurrent glioblastoma (GBM): An Ivy Foundation early-phase clinical trials consortium study.
Cloughesy T, Mischel P, Omuro A, Prados M, Wen P, Wu B, Rockich K, Xu Y, Lager J, Mellinghoff I. Tumor pharmacokinetics (PK) and pharmacodynamics (PD) of SAR245409 (XL765) and SAR245408 (XL147) administered as single agents to patients with recurrent glioblastoma (GBM): An Ivy Foundation early-phase clinical trials consortium study. Journal Of Clinical Oncology 2013, 31: 2012-2012. DOI: 10.1200/jco.2013.31.15_suppl.2012.Peer-Reviewed Original ResearchPan-PI3K inhibitorCohort 1Cohort 2Frozen tumor tissueTumor tissueTumor samplesK inhibitorsArchived tumor samplesPK/PD analysisPI3K/mTOR pathwayPD analysisTreatment of glioblastomaInhibition of proliferationPI3K inhibitorsPharmacodynamic impactEarly surgeryLast doseSurgical resectionCNS tumorsMean tumorRecurrent glioblastomaTumor resectionFFPE tumor samplesPK analysisCohort 3