2021
CTNI-18. PHASE I AND PRELIMINARY PHASE 0 RESULTS OF ABTC 1801: A MULTI-ARM CLINICAL TRIAL OF THE PARP INHIBITOR PAMIPARIB (BGB290) WITH VERY LOW DOSE METRONOMIC TEMOZOLOMIDE IN RECURRENT IDH MUTANT GLIOMAS
Schiff D, Bindra R, Li J, Ye X, Ellingson B, Walbert T, Campian J, Nabors L, Lieberman F, Ozer B, Desai A, Omuro A, Wen P, Desideri S, Fisher J, Grossman S. CTNI-18. PHASE I AND PRELIMINARY PHASE 0 RESULTS OF ABTC 1801: A MULTI-ARM CLINICAL TRIAL OF THE PARP INHIBITOR PAMIPARIB (BGB290) WITH VERY LOW DOSE METRONOMIC TEMOZOLOMIDE IN RECURRENT IDH MUTANT GLIOMAS. Neuro-Oncology 2021, 23: vi63-vi63. DOI: 10.1093/neuonc/noab196.243.Peer-Reviewed Original ResearchMetronomic temozolomidePhase IFavorable brain penetrationDose level 1Phase II studyGrade 2 neutropeniaArm clinical trialKPS 90Inadequate dosingPrior radiotherapyAlkylator therapyHematological toxicityII studyMedian ageAdditional patientsStudy treatmentBrain penetrationRelapse 3BRCAness phenotypeClinical trialsIDH1 mutant gliomasSurgical armTemozolomide dosePreclinical studiesAnaplastic astrocytoma
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
2018
Multicenter Phase IB Trial of Carboxyamidotriazole Orotate and Temozolomide for Recurrent and Newly Diagnosed Glioblastoma and Other Anaplastic Gliomas.
Omuro A, Beal K, McNeill K, Young RJ, Thomas A, Lin X, Terziev R, Kaley TJ, DeAngelis LM, Daras M, Gavrilovic IT, Mellinghoff I, Diamond EL, McKeown A, Manne M, Caterfino A, Patel K, Bavisotto L, Gorman G, Lamson M, Gutin P, Tabar V, Chakravarty D, Chan TA, Brennan CW, Garrett-Mayer E, Karmali RA, Pentsova E. Multicenter Phase IB Trial of Carboxyamidotriazole Orotate and Temozolomide for Recurrent and Newly Diagnosed Glioblastoma and Other Anaplastic Gliomas. Journal Of Clinical Oncology 2018, 36: 1702-1709. PMID: 29683790, PMCID: PMC5993168, DOI: 10.1200/jco.2017.76.9992.Peer-Reviewed Original ResearchConceptsAnaplastic gliomasCohort 2Cohort 1Median progression-free survivalFavorable brain penetrationMedian overall survivalPhase Ib studyPhase Ib trialPhase II doseProgression-free survivalRecurrent anaplastic gliomasDependent calcium channelsNovel oral inhibitorSignal of activityMismatch repair genesIb trialTreat populationMethylguanine-DNA methyltransferaseOverall survivalComplete responseFlat doseOral inhibitorBrain penetrationResults FortyTherapeutic concentrations