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
2014
PHASE II TRIAL OF THE PHOSPHATIDYINOSITOL-3 KINASE (PI3K) INHIBITOR BUPARLISIB (BKM120) IN RECURRENT GLIOBLASTOMA CONDUCTED BY THE IVY FOUNDATION EARLY PHASE CLINICAL TRIALS CONSORTIUM
Wen P, Wen P, Yung W, Mellinghoff I, Ramkissoon S, Alexander B, Rinne M, Colman H, Omuro A, DeAngelis L, Gilbert M, DeGroot J, Cloughesy T, Lee E, Nayak L, S. A, Batchelor T, Chang S, Prados M, Reardon D, Ligon K. PHASE II TRIAL OF THE PHOSPHATIDYINOSITOL-3 KINASE (PI3K) INHIBITOR BUPARLISIB (BKM120) IN RECURRENT GLIOBLASTOMA CONDUCTED BY THE IVY FOUNDATION EARLY PHASE CLINICAL TRIALS CONSORTIUM. Neuro-Oncology 2014, 16: iii47-iii47. PMCID: PMC4144634, DOI: 10.1093/neuonc/nou209.20.Peer-Reviewed Original ResearchPI3K pathwayCohort 2Cohort 1Pan-class I PI3K inhibitorEnzyme-inducing antiepileptic drugsAdequate bone marrowGrade 4 toxicityGrowth of U87K pathwayGrade 3 toxicityPhase II studyPhase II trialRecurrent GBM patientsAdditional eligibility criteriaALT/ASTSingle-agent efficacyPotential therapeutic targetPI3K mutationsReduction of pAKTPI3K inhibitorsEvaluable patientsMedian OSMedian PFSPrior bevacizumabRadiologic progression
2013
Phase II trial of the phosphatidyinositol-3 kinase (PI3K) inhibitor BKM120 in recurrent glioblastoma (GBM).
Wen P, Yung W, Mellinghoff I, Lamborn K, Ramkissoon S, Cloughesy T, Rinne M, Omuro A, DeAngelis L, Gilbert M, Chi A, Batchelor T, Colman H, Chang S, Massacesi C, DiTomaso E, Prados M, Reardon D, Ligon K. Phase II trial of the phosphatidyinositol-3 kinase (PI3K) inhibitor BKM120 in recurrent glioblastoma (GBM). Journal Of Clinical Oncology 2013, 31: 2015-2015. DOI: 10.1200/jco.2013.31.15_suppl.2015.Peer-Reviewed Original ResearchPI3K pathwayRecurrent glioblastomaK pathwayPan-class I PI3K inhibitorMajor grade 3/4 toxicitiesEnzyme-inducing antiepileptic drugsAdequate bone marrowGrade 3/4 toxicitiesPhase II studyPhase II trialProgression-free survivalClinical Trials ConsortiumRecurrent GBM patientsAdditional eligibility criteriaPotential therapeutic targetReduction of pAKTWhole-exome sequencingPI3K inhibitorsAnalysis of tumorsRadiologic progressionUnresectable glioblastomaII trialPrimary endpointRecurrent diseaseII studyPhase 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