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 pharmacokineticsVoxtalisibPatients
2014
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
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