2024
A phase (Ph) 0/Ia study of brigimadlin concentration in brain tissue and a non-randomized, open-label, dose escalation study of brigimadlin in combination with radiotherapy (RT) in patients (pts) with newly diagnosed glioblastoma (GBM).
Sarkaria J, Mrugala M, Jaeckle K, Burns T, Vaubel R, Parney I, Chaichana K, Clement P, Martinez-Garcia M, Sepulveda Sanchez J, Omuro A, Pronk L, Ross H, Teufel M, Hesse R, Grempler R, Galanis E. A phase (Ph) 0/Ia study of brigimadlin concentration in brain tissue and a non-randomized, open-label, dose escalation study of brigimadlin in combination with radiotherapy (RT) in patients (pts) with newly diagnosed glioblastoma (GBM). Journal Of Clinical Oncology 2024, 42: 2017-2017. DOI: 10.1200/jco.2024.42.16_suppl.2017.Peer-Reviewed Original ResearchNon-contrast-enhancedOpen-labelContrast enhancementMGMT promoter unmethylated glioblastomaUnbound concentrationsCalculated unbound concentrationsNewly diagnosed GBMDose-escalation studyMaximum tolerated doseTumor cell apoptosisSingle-arm trialMDM2-p53 antagonistsRestore wild-typeBrain tissueUnmethylated glioblastomaBrain tumor tissueEscalation studyDiagnosed glioblastomaTolerated doseP53 target gene expressionPrimary endpointIDH-wtSolid tumorsTumor tissuesXenograft model
2017
Multicenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy With Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma
Clarke J, Neil E, Terziev R, Gutin P, Barani I, Kaley T, Lassman AB, Chan TA, Yamada J, DeAngelis L, Ballangrud A, Young R, Panageas KS, Beal K, Omuro A. Multicenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy With Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma. International Journal Of Radiation Oncology • Biology • Physics 2017, 99: 797-804. PMID: 28870792, PMCID: PMC5654655, DOI: 10.1016/j.ijrobp.2017.06.2466.Peer-Reviewed Original ResearchMeSH KeywordsAgedAngiogenesis InhibitorsAstrocytomaBevacizumabBrainBrain NeoplasmsFemaleGlioblastomaHumansIntention to Treat AnalysisKarnofsky Performance StatusMaleMaximum Tolerated DoseMiddle AgedNeoplasm Recurrence, LocalOrgans at RiskProspective StudiesRadiation Dose HypofractionationRadiosurgeryRe-IrradiationTumor BurdenConceptsRecurrent high-grade gliomaDose-limiting toxicityHigh-grade gliomasStereotactic reirradiationHypofractionated Stereotactic Radiation TherapyCorpus callosum involvementDose level cohortsGrade 3 fatigueMedian overall survivalKarnofsky performance statusDose-escalation studyTreatment-related effectsBiological equivalent doseStereotactic radiation therapyWarrants further investigationAbsence of brainstemDose-escalation trial designBevacizumab dosesCallosum involvementConcomitant bevacizumabSymptomatic radionecrosisEscalation studyOverall survivalPerformance statusResected specimens
2015
Phase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma
Wen PY, Omuro A, Ahluwalia MS, Fathallah-Shaykh HM, Mohile N, Lager JJ, Laird AD, Tang J, Jiang J, Egile C, Cloughesy TF. Phase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma. Neuro-Oncology 2015, 17: 1275-1283. PMID: 26019185, PMCID: PMC4588757, DOI: 10.1093/neuonc/nov083.Peer-Reviewed Original ResearchConceptsHigh-grade gliomasAdverse eventsRadiation therapySkin biopsiesPhase I dose-escalation studyTreatment-related adverse eventsI dose-escalation studyPI3K/mTOR pathway inhibitionTreatment-related gradeDose-escalation studyDose-escalation designFavorable safety profileMTOR pathway inhibitionEvaluable patientsStable diseasePartial responsePharmacodynamic effectsPlatelet countRapamycin inhibitorsSafety profilePreliminary efficacyTumor responsePlasma pharmacokineticsVoxtalisibPatientsMulticenter Phase I Dose Escalation Study of Hypofractionated Stereotactic Radiotherapy with Bevacizumab in the Treatment of Recurrent Malignant Glioma (S43.005)
Neil E, Clarke J, Beal K, Gutin P, Igor B, Kaley T, Lassman A, Perezic-Mustafa M, Young R, Omuro A. Multicenter Phase I Dose Escalation Study of Hypofractionated Stereotactic Radiotherapy with Bevacizumab in the Treatment of Recurrent Malignant Glioma (S43.005). Neurology 2015, 84 DOI: 10.1212/wnl.84.14_supplement.s43.005.Peer-Reviewed Original Research