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
2016
ACTR-12. PHASE I/II STUDY OF SINGLE AGENT IBRUTINIB IN RECURRENT/REFRACTORY PRIMARY (PCNSL) AND SECONDARY CNS LYMPHOMA (SCNSL)
Grommes C, Gavrilovic I, Kaley T, Nolan C, Omuro A, Wolfe J, Pentsova E, Hatzoglou V, Mellinghoff I, DeAngelis L. ACTR-12. PHASE I/II STUDY OF SINGLE AGENT IBRUTINIB IN RECURRENT/REFRACTORY PRIMARY (PCNSL) AND SECONDARY CNS LYMPHOMA (SCNSL). Neuro-Oncology 2016, 18: vi3-vi4. DOI: 10.1093/neuonc/now212.011.Peer-Reviewed Original ResearchSecondary CNS lymphomaCNS lymphomaPhase I/II studyRecurrent/refractory diseaseAggressive primary brain tumorCerebrospinal fluid involvementCNS lymphoma patientsGrade 4 toxicityGrade 3 toxicityEnd-organ functionNormal end-organ functionSingle-agent ibrutinibPrimary brain tumorsPromising clinical responsesB-cell malignanciesCommon toxicitiesEligible patientsFungal encephalitisManageable toxicityMedian PFSMethotrexate regimensPrior therapySCNSL patientsClinical responseII studyMPTH-01. ARE MUTATIONS IN MISMATCH REPAIR (MMR) GENES OUR NEXT BIOMARKER OF ALKYLATING AGENT INDUCED HYPERMUTATOR PHENOTYPE? PRELIMINARY RESULTS FROM THE IVY PRECISION TRIAL
Kuhn J, Chen R, Clarke J, Chang S, Cloughesy T, Colman H, Wen P, Mellinghoff I, Ligon K, de Groot J, Batchelor T, Omuro A, Taylor J, Butowski N, Halperin R, Tran N, Carpten J, Craig D, Byron S, Berens M, Prados M. MPTH-01. ARE MUTATIONS IN MISMATCH REPAIR (MMR) GENES OUR NEXT BIOMARKER OF ALKYLATING AGENT INDUCED HYPERMUTATOR PHENOTYPE? PRELIMINARY RESULTS FROM THE IVY PRECISION TRIAL. Neuro-Oncology 2016, 18: vi105-vi105. DOI: 10.1093/neuonc/now212.440.Peer-Reviewed Original ResearchIDH1 mutationMMR mutationsPRECISION trialHypermutator phenotypeMutation/lossClinical Trials ConsortiumHigh neoantigen loadRecurrent GBM tumorsWhole-exome sequencingMMR alterationsNext biomarkersPrior therapySpecific immunotherapyNeoantigen loadRecurrent GBMPhenotype patientsTumor boardMutational loadPatientsProgressive gliomasMGMT statusMLH1 mutationsGBM tumorsTherapeutic opportunitiesTumors
2015
Outcomes of Pharmacokinetically (PK) Directed Busulfan in Combination with Thiotepa & Cyclophosphamide (TBC) Conditioning with HDT-ASCT in Patients with Primary & Secondary CNS Lymphoma
Bhatt V, Scordo M, Hsu M, Omuro A, DeAngelis L, Lin A, Matasar M, Dahi P, Moskowitz C, Giralt S, Sauter C. Outcomes of Pharmacokinetically (PK) Directed Busulfan in Combination with Thiotepa & Cyclophosphamide (TBC) Conditioning with HDT-ASCT in Patients with Primary & Secondary CNS Lymphoma. Blood 2015, 126: 1994. DOI: 10.1182/blood.v126.23.1994.1994.Peer-Reviewed Original ResearchHDT-ASCTIdeal body weightComplete remissionPartial remissionBody weightBusulfan/cyclophosphamide conditioningAutologous stem cell transplantationSecondary CNS lymphomaTransplant related mortalityHigh-dose therapyStem cell infusionStem cell transplantationBU AUCCyclophosphamide conditioningHCT-CIChemosensitive patientsFirst remissionPrior therapyRemission inductionCNS lymphomaFirst doseTarget AUCCell infusionMedian ageDosage adjustment
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 vinorelbine and intensive temozolomide for patients with recurrent or progressive brain metastases
Iwamoto FM, Omuro AM, Raizer JJ, Nolan CP, Hormigo A, Lassman AB, Gavrilovic IT, Abrey LE. A phase II trial of vinorelbine and intensive temozolomide for patients with recurrent or progressive brain metastases. Journal Of Neuro-Oncology 2007, 87: 85-90. PMID: 17987262, DOI: 10.1007/s11060-007-9491-3.Peer-Reviewed Original ResearchConceptsKarnofsky Performance ScaleProgressive brain metastasesPhase II trialBrain metastasesII trialResponse rateMedian Karnofsky performance scaleWhole-brain radiation therapyAdequate organ functionBrain metastasis resectionObjective radiographic responseRadiographic response rateSingle-agent temozolomideGrade 3/4 toxicitiesRecurrent brain metastasesPopulation of patientsPrimary tumor siteYears of agePrior therapyStable diseaseVinorelbine 25Metastasis resectionPrimary endpointMethods PatientsOverall survivalA 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