2012
A Multicenter Phase I Trial of PX-866, an Oral Irreversible Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Advanced Solid Tumors
Hong DS, Bowles DW, Falchook GS, Messersmith WA, George GC, O'Bryant CL, Vo AC, Klucher K, Herbst RS, Eckhardt SG, Peterson S, Hausman DF, Kurzrock R, Jimeno A. A Multicenter Phase I Trial of PX-866, an Oral Irreversible Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Advanced Solid Tumors. Clinical Cancer Research 2012, 18: 4173-4182. PMID: 22693357, DOI: 10.1158/1078-0432.ccr-12-0714.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAged, 80 and overArea Under CurveDiarrheaDisease ProgressionDose-Response Relationship, DrugDrug Administration ScheduleEnzyme InhibitorsFatigueFemaleGonanesHumansMaleMetabolic Clearance RateMiddle AgedMutationNauseaNeoplasmsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsTreatment OutcomeVomitingConceptsDose-limiting toxicityArm 1PX-866Stable diseaseArm 2Frequent study drug-related adverse eventsSolid tumorsStudy drug-related adverse eventsDrug-related adverse eventsMulticenter phase I trialGrade III diarrheaAdvanced solid tumorsDose-escalation studyResponse Evaluation CriteriaContinuous dosing scheduleElevated aspartate aminotransferasePhase I trialEvaluable patientsIrreversible small-molecule inhibitorAdverse eventsDosing schedulesI trialAdditional patientsGastrointestinal disordersIncurable cancer
2009
Phase I trial of PX-866, a novel phosphoinositide-3-kinase (PI-3K) inhibitor
Jimeno A, Hong D, Hecker S, Clement R, Kurzrock R, Pestano L, Hiscox A, Leos R, Kirkpatrick D, Eckhardt S, Herbst R. Phase I trial of PX-866, a novel phosphoinositide-3-kinase (PI-3K) inhibitor. Journal Of Clinical Oncology 2009, 27: 3542-3542. DOI: 10.1200/jco.2009.27.15_suppl.3542.Peer-Reviewed Original ResearchPX-866Stable diseaseClinical trialsDay 1Drug-related severe adverse eventsMild side effect profilePhase 1 clinical trialStabilization of diseaseSevere adverse eventsDose-limiting toxicityPhase I trialSide effect profileAdvanced metastatic cancerP-mTOR levelsDose-dependent inhibitionLower drug dosesPhosphoinositide-3 kinase inhibitorPD endpointsExpansion cohortLast doseAbdominal discomfortAdverse eventsI trialEffect profileLoss of PTEN
2008
Dose Escalation of Gemcitabine Is Possible With Concurrent Chest Three-Dimensional Rather Than Two-Dimensional Radiotherapy: A Phase I Trial in Patients With Stage III Non–Small-Cell Lung Cancer
Zinner RG, Komaki R, Cox JD, Glisson BS, Pisters KM, Herbst RS, Kies M, Liao Z, Hong WK, Fossella FV. Dose Escalation of Gemcitabine Is Possible With Concurrent Chest Three-Dimensional Rather Than Two-Dimensional Radiotherapy: A Phase I Trial in Patients With Stage III Non–Small-Cell Lung Cancer. International Journal Of Radiation Oncology • Biology • Physics 2008, 73: 119-127. PMID: 18556142, DOI: 10.1016/j.ijrobp.2008.03.069.Peer-Reviewed Original ResearchMeSH KeywordsAbdomenAdultAgedAged, 80 and overAntimetabolites, AntineoplasticCarcinoma, Non-Small-Cell LungCombined Modality TherapyDeoxycytidineDose-Response Relationship, DrugDose-Response Relationship, RadiationFeasibility StudiesFemaleGemcitabineHumansLung NeoplasmsMaleMiddle AgedRadiation-Sensitizing AgentsRadiotherapy, ConformalTreatment OutcomeConceptsGrade 3 esophagitisDose of gemcitabineCell lung cancerTwo-dimensional radiotherapyLung cancerThree-dimensional conformal radiotherapySevere acute esophagitisWeekly gemcitabine concurrentCycles of gemcitabinePhase II doseStage III NSCLCDose-limiting toxicityPhase I trialThree-dimensional CRTChest radiotherapyConcurrent chestConcurrent radiotherapySevere esophagitisAcute esophagitisI trialDose escalationConformal radiotherapyEsophagitisApparent diseaseStage IIIClinical, pharmacokinetic (PK), pharmacodynamic findings in a phase I trial of weekly (wkly) intravenous AZD4877 in patients with refractory solid tumors
Infante J, Spratlin J, Kurzrock R, Eckhardt S, Burris H, Puchalski T, Li J, Wu K, Ochs J, Herbst R. Clinical, pharmacokinetic (PK), pharmacodynamic findings in a phase I trial of weekly (wkly) intravenous AZD4877 in patients with refractory solid tumors. Journal Of Clinical Oncology 2008, 26: 2501-2501. DOI: 10.1200/jco.2008.26.15_suppl.2501.Peer-Reviewed Original Research
2007
The changing face of phase I protocols: A closer look at study requirements
Craft B, Kurzrock R, Herbst R, Culotta K, Stewart C, Dorsey V, Lippman S, Gingher D, Bekele N, Karp D. The changing face of phase I protocols: A closer look at study requirements. Journal Of Clinical Oncology 2007, 25: 3061-3061. DOI: 10.1200/jco.2007.25.18_suppl.3061.Peer-Reviewed Original ResearchClinical Translational Research CenterPhase II trialPhase I clinical trialPhase I trialII trialClinical trialsPhase II trialMedical oncologyTranslational Research CenterCancer clinical trialsCurrent phase ILate-phase studiesPhase I programSame time periodTherapeutic requirementsECG monitoringTrialsSignificant financial relationshipElectrocardiographyStudy requirementsOncologyStudy complexityI programMore PKPhase I participants’ views of quality of life and trial participation burdens
Cohen MZ, Slomka J, Pentz RD, Flamm AL, Gold D, Herbst RS, Abbruzzese JL. Phase I participants’ views of quality of life and trial participation burdens. Supportive Care In Cancer 2007, 15: 885-890. PMID: 17252219, DOI: 10.1007/s00520-007-0216-0.Peer-Reviewed Original ResearchConceptsTrial participationCurrent QoLPrevious cancer treatmentPhase I trialPhase I cancer trialsI cancer trialsSymptoms of diseaseStudy drugI trialCancer trialsPhysical complicationsTrial participantsSide effectsQoLCancer treatmentPhase ITrialsPotential participantsBurdenPerception of qualityProcedural burdenRespondent burdenParticipantsTreatmentBaseline ability
2002
Study of the media's potential influence on prospective research participants' understanding of and motivations for participation in a high-profile phase I trial.
Pentz RD, Flamm AL, Sugarman J, Cohen MZ, Daniel Ayers G, Herbst RS, Abbruzzese JL. Study of the media's potential influence on prospective research participants' understanding of and motivations for participation in a high-profile phase I trial. Journal Of Clinical Oncology 2002, 20: 3785-91. PMID: 12228198, DOI: 10.1200/jco.2002.04.084.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsAttitude to HealthClinical Trials, Phase I as TopicCollagenData CollectionDecision MakingEndostatinsFemaleHumansInformed ConsentMaleMass MediaMiddle AgedMotivationNeoplasmsPatient ParticipationPeptide FragmentsPhysiciansProspective StudiesResearch DesignSurveys and QuestionnairesConceptsPercent of respondentsPhase I clinical trialPhase I trialHuman recombinant endostatinI trialClinical trialsTrial investigatorsResearch participants' understandingTrialsEndostatinPhysiciansRecombinant endostatinPotential influencePercentProspective participantsTrial purposesSurvey respondentsPersonal benefitsParticipants' understandingPatientsRespondentsPhase I study of recombinant human endostatin in patients with advanced solid tumors.
Herbst RS, Hess KR, Tran HT, Tseng JE, Mullani NA, Charnsangavej C, Madden T, Davis DW, McConkey DJ, O’Reilly M, Ellis LM, Pluda J, Hong WK, Abbruzzese JL. Phase I study of recombinant human endostatin in patients with advanced solid tumors. Journal Of Clinical Oncology 2002, 20: 3792-803. PMID: 12228199, DOI: 10.1200/jco.2002.11.061.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAngiogenesis InhibitorsCollagenCollagen Type XVIIIEndostatinsEndothelial Growth FactorsE-SelectinFemaleFibroblast Growth Factor 2Hematologic DiseasesHumansImmunoglobulinsInfusions, IntravenousLymphokinesMagnetic Resonance ImagingMaleMaximum Tolerated DoseMiddle AgedNeoplasmsPeptide FragmentsRecombinant ProteinsTime FactorsTissue DistributionVascular Cell Adhesion Molecule-1Vascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsRh-EndoConcentration-time curveRecombinant human endostatinSerum markersPreclinical modelsSolid tumorsHuman endostatinDose-limiting toxic effectAntitumor activityTwo-compartmental open modelAdvanced solid tumorsPhase I trialCentral line accessDose-finding trialMinor antitumor activityI trialIntravenous bolusSerum biomarkersSerum antibodiesPharmacokinetic dispositionAllergic reactionsPatientsPharmacokinetic profileDose levelsPhase ISelective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trial.
Herbst RS, Maddox AM, Rothenberg ML, Small EJ, Rubin EH, Baselga J, Rojo F, Hong WK, Swaisland H, Averbuch SD, Ochs J, LoRusso PM. Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trial. Journal Of Clinical Oncology 2002, 20: 3815-25. PMID: 12228201, DOI: 10.1200/jco.2002.03.038.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAged, 80 and overAntineoplastic AgentsCarcinoma, Non-Small-Cell LungDose-Response Relationship, DrugDrug Administration ScheduleEnzyme InhibitorsFemaleGastrointestinal DiseasesGefitinibHead and Neck NeoplasmsHumansLung NeoplasmsMaleMaximum Tolerated DoseMiddle AgedNeoplasm StagingNeoplasmsProtein-Tyrosine KinasesQuinazolinesSkin DiseasesConceptsDose-limiting toxicityPharmacokinetic analysisEpidermal growth factor receptor tyrosine kinase inhibitor ZD1839Epidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsGrade 1/2 adverse eventsTyrosine kinase inhibitor ZD1839Primary dose-limiting toxicityReceptor tyrosine kinase inhibitorsPrior cancer therapyAntitumor activityDaily oral dosingPhase I trialCell lung cancerTyrosine kinase inhibitorsSolid tumor typesVariability of exposureStable diseaseAdverse eventsPartial responseUndue toxicityI trialTolerability trialCell lungFollicular rash
2001
Gemcitabine and vinorelbine in patients with advanced lung cancer: preclinical studies and report of a phase I trial
Herbst R, Lynch C, Vasconcelles M, Teicher B, Strauss G, Elias A, Anderson I, Zacarola P, Dang N, Leong T, Salgia R, Skarin A. Gemcitabine and vinorelbine in patients with advanced lung cancer: preclinical studies and report of a phase I trial. Cancer Chemotherapy And Pharmacology 2001, 48: 151-159. PMID: 11561781, DOI: 10.1007/s002800100282.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerAdvanced lung cancerDana-Farber Cancer InstituteLung cancerDose levelsMouse Lewis lung cancer modelLewis lung cancer modelMedian ECOG performance statusMouse Lewis lung carcinoma modelPhase I clinical studyDay 15 doseDose level 4ECOG performance statusLewis lung carcinoma modelCentral venous lineEfficacy of gemcitabinePhase I trialCell lung cancerLung cancer modelAbility of patientsHighest dose levelLung carcinoma modelHematologic toxicityChemotherapeutic regimenI trialClinical studies of angiogenesis inhibitors: The university of texas md anderson center trial of human endostatin
Herbst R, Lee A, Tran H, Abbruzzese J. Clinical studies of angiogenesis inhibitors: The university of texas md anderson center trial of human endostatin. Current Oncology Reports 2001, 3: 131-140. PMID: 11177745, DOI: 10.1007/s11912-001-0013-8.Peer-Reviewed Original ResearchConceptsPhase I trialI trialClinical studiesHuman endostatinTumor vasculatureSolid tumor malignanciesAnti-angiogenic agentsAnti-angiogenic mechanismAnti-angiogenic compoundsToxic cancer treatmentsAdvanced diseaseBlood vessel supplyCenter trialMinimal diseaseTumor sizeNovel agentsSurrogate endpointsNew agentsSide effectsBiologic mechanismsSingle agentAngiogenesis inhibitorsGrowth-inhibiting moleculesNon-toxic agentsTumor growth
2000
Gemcitabine (G) with concurrent chest radiation (XRT) followed by consolidation chemotherapy with gemcitabine plus cisplatin (CDDP): A phase I trial for patients with stage III non-small cell lung cancer (NSCLC)
Fossella F, Zinner R, Komaki R, Jung M, Jhingran A, Glisson B, Pisters K, Stevens C, Khuri F, Kurie J, Lee J, Herbst R, Liao Z, Hong W. Gemcitabine (G) with concurrent chest radiation (XRT) followed by consolidation chemotherapy with gemcitabine plus cisplatin (CDDP): A phase I trial for patients with stage III non-small cell lung cancer (NSCLC). Lung Cancer 2000, 29: 111-112. DOI: 10.1016/s0169-5002(00)80369-4.Peer-Reviewed Original ResearchObjective regressions in non-small cell lung cancer patients treated in Phase I trials of oral ZD1839 (IressaTM), a selective tyrosine kinase inhibitor that blocks the epidermal growth factor receptor (EGFR)
Kris M, Herbst R, Rischin D, LoRusso P, Baselga J, Hammond L, Feyereislova A, Ochs J, Averbuch S. Objective regressions in non-small cell lung cancer patients treated in Phase I trials of oral ZD1839 (IressaTM), a selective tyrosine kinase inhibitor that blocks the epidermal growth factor receptor (EGFR). Lung Cancer 2000, 29: 72. DOI: 10.1016/s0169-5002(00)80233-0.Peer-Reviewed Original ResearchEpidermal growth factor receptorNon-small cell lung cancer patientsCell lung cancer patientsPhase I trialSelective tyrosine kinase inhibitorLung cancer patientsTyrosine kinase inhibitorsGrowth factor receptorObjective regressionI trialCancer patientsOral ZD1839Kinase inhibitorsFactor receptorPatientsZD1839